SitesBLAST
Comparing GFF373 PGA1_c03840 methylmalonyl-CoA mutase large subunit to proteins with known functional sites using BLASTp with E ≤ 0.001.
Or try Sites on a Tree, PaperBLAST, Conserved Domains, or compare to all protein structures
Found 20 (the maximum) hits to proteins with known functional sites (download)
6oxdA Structure of mycobacterium tuberculosis methylmalonyl-coa mutase with adenosyl cobalamin (see paper)
37% identity, 99% coverage: 2:649/655 of query aligns to 87:731/736 of 6oxdA
- active site: Y100 (= Y15), Y254 (= Y169), H255 (= H170), K610 (= K528), D614 (= D532), H616 (= H534)
- binding cobalamin: Y100 (= Y15), L130 (= L45), H133 (≠ Q48), A150 (≠ V65), R218 (= R133), E258 (= E173), G344 (≠ S262), W345 (≠ L263), E381 (= E302), A382 (= A303), A384 (≠ G305), L385 (= L306), G615 (= G533), H616 (= H534), D617 (≠ S535), R618 (≠ N536), S661 (= S579), L663 (= L581), A665 (≠ G583), G691 (= G609), G692 (= G610), F711 (≠ Y629), P712 (≠ T630), T715 (≠ D633)
- binding Itaconyl coenzyme A: T88 (≠ Q3), M89 (= M4), Q93 (≠ R8), T96 (≠ L11), R98 (= R13), Y100 (= Y15), S175 (= S90), T177 (= T92), T206 (= T121), R218 (= R133), H255 (= H170), R294 (= R211), S296 (= S213), F298 (= F215), R337 (= R255), T338 (≠ Y256), H339 (≠ G257), Q341 (= Q259), Q372 (≠ R293)
Sites not aligning to the query:
7reqA Methylmalonyl-coa mutase, 2-carboxypropyl-coa inhibitor complex (see paper)
36% identity, 96% coverage: 4:631/655 of query aligns to 75:704/725 of 7reqA
- active site: Y86 (= Y15), Y240 (= Y169), H241 (= H170), K601 (= K528), D605 (= D532), H607 (= H534)
- binding 2-carboxypropyl-coenzyme a: M75 (= M4), F78 (≠ D7), R79 (= R8), T82 (≠ L11), R84 (= R13), Y86 (= Y15), S161 (= S90), T163 (= T92), T192 (= T121), R204 (= R133), H241 (= H170), R280 (= R211), S282 (= S213), F284 (= F215), H325 (≠ G257), Q358 (≠ R293)
- binding cobalamin: Y86 (= Y15), L116 (= L45), A136 (≠ V65), R204 (= R133), E244 (= E173), G330 (≠ S262), W331 (≠ L263), E367 (= E302), A368 (= A303), A370 (≠ G305), G606 (= G533), H607 (= H534), D608 (≠ S535), R609 (≠ N536), G610 (= G537), I614 (= I541), S652 (= S579), L654 (= L581), G682 (= G609), G683 (= G610), Y702 (= Y629), T703 (= T630)
Sites not aligning to the query:
3reqA Methylmalonyl-coa mutase, substrate-free state (poor quality structure) (see paper)
36% identity, 96% coverage: 4:631/655 of query aligns to 75:704/725 of 3reqA
- active site: Y86 (= Y15), Y240 (= Y169), H241 (= H170), K601 (= K528), D605 (= D532), H607 (= H534)
- binding adenosine: Y86 (= Y15), Y240 (= Y169), E244 (= E173), G330 (≠ S262)
- binding cobalamin: L116 (= L45), V203 (≠ S132), R204 (= R133), E244 (= E173), G330 (≠ S262), W331 (≠ L263), A368 (= A303), G606 (= G533), H607 (= H534), D608 (≠ S535), R609 (≠ N536), G610 (= G537), I614 (= I541), G650 (= G577), S652 (= S579), L654 (= L581), G682 (= G609), G683 (= G610), Y702 (= Y629), T703 (= T630), P704 (= P631)
Sites not aligning to the query:
2reqA Methylmalonyl-coa mutase, non-productive coa complex, in open conformation representing substrate-free state (see paper)
36% identity, 96% coverage: 4:631/655 of query aligns to 75:704/725 of 2reqA
- active site: Y86 (= Y15), Y240 (= Y169), H241 (= H170), K601 (= K528), D605 (= D532), H607 (= H534)
- binding cobalamin: V203 (≠ S132), R204 (= R133), E244 (= E173), A245 (= A174), W331 (≠ L263), A368 (= A303), G606 (= G533), H607 (= H534), D608 (≠ S535), R609 (≠ N536), G610 (= G537), I614 (= I541), G650 (= G577), S652 (= S579), L654 (= L581), A655 (≠ S582), G682 (= G609), G683 (= G610), Y702 (= Y629), T703 (= T630)
- binding coenzyme a: R79 (= R8), K318 (= K250)
Sites not aligning to the query:
4reqA Methylmalonyl-coa mutase substrate complex (see paper)
36% identity, 96% coverage: 4:631/655 of query aligns to 76:705/726 of 4reqA
- active site: Y87 (= Y15), Y241 (= Y169), H242 (= H170), K602 (= K528), D606 (= D532), H608 (= H534)
- binding cobalamin: Y87 (= Y15), L117 (= L45), A137 (≠ V65), V204 (≠ S132), R205 (= R133), H242 (= H170), E245 (= E173), G331 (≠ S262), W332 (≠ L263), E368 (= E302), A369 (= A303), A371 (≠ G305), L372 (= L306), G607 (= G533), H608 (= H534), D609 (≠ S535), R610 (≠ N536), G611 (= G537), I615 (= I541), S653 (= S579), L655 (= L581), G683 (= G609), G684 (= G610), V685 (≠ I611), Y703 (= Y629), T704 (= T630)
- binding methylmalonyl-coenzyme a: M76 (= M4), F79 (≠ D7), R80 (= R8), T83 (≠ L11), R85 (= R13), Y87 (= Y15), S112 (= S40), S162 (= S90), T164 (= T92), T193 (= T121), R205 (= R133), N234 (= N162), Y241 (= Y169), H242 (= H170), R281 (= R211), S283 (= S213), F285 (= F215), H326 (≠ G257), Q328 (= Q259), Q359 (≠ R293), S360 (≠ A294)
- binding succinyl-coenzyme a: M76 (= M4), F79 (≠ D7), R80 (= R8), T83 (≠ L11), R85 (= R13), Y87 (= Y15), S162 (= S90), T164 (= T92), T193 (= T121), Q195 (= Q123), R205 (= R133), N234 (= N162), Y241 (= Y169), H242 (= H170), R281 (= R211), S283 (= S213), F285 (= F215), R324 (= R255), H326 (≠ G257), Q359 (≠ R293)
Sites not aligning to the query:
6reqA Methylmalonyl-coa mutase, 3-carboxypropyl-coa inhibitor complex (see paper)
36% identity, 96% coverage: 4:631/655 of query aligns to 77:706/727 of 6reqA
- active site: Y88 (= Y15), Y242 (= Y169), H243 (= H170), K603 (= K528), D607 (= D532), H609 (= H534)
- binding 3-carboxypropyl-coenzyme a: M77 (= M4), F80 (≠ D7), R81 (= R8), T84 (≠ L11), R86 (= R13), Y88 (= Y15), S113 (= S40), S163 (= S90), T165 (= T92), T194 (= T121), R206 (= R133), H243 (= H170), R282 (= R211), S284 (= S213), F286 (= F215), H327 (≠ G257), Q329 (= Q259), Q360 (≠ R293)
- binding cobalamin: Y88 (= Y15), F116 (= F43), L118 (= L45), H121 (≠ Q48), A138 (≠ V65), R206 (= R133), E246 (= E173), G332 (≠ S262), W333 (≠ L263), E369 (= E302), A370 (= A303), A372 (≠ G305), G608 (= G533), H609 (= H534), D610 (≠ S535), R611 (≠ N536), G612 (= G537), I616 (= I541), Y620 (≠ A545), S654 (= S579), L656 (= L581), G658 (= G583), G684 (= G609), G685 (= G610), Y704 (= Y629), T705 (= T630)
Sites not aligning to the query:
P11653 Methylmalonyl-CoA mutase large subunit; MCM-alpha; EC 5.4.99.2 from Propionibacterium freudenreichii subsp. shermanii (see 4 papers)
36% identity, 96% coverage: 4:631/655 of query aligns to 78:707/728 of P11653
- M78 (= M4) binding
- R82 (= R8) binding
- T85 (≠ L11) binding
- R87 (= R13) binding
- Y89 (= Y15) binding ; mutation to F: Does not significantly affect affinity for succiny-CoA, but kcat is lowered about 580-fold.
- S114 (= S40) binding
- F117 (= F43) binding
- A139 (≠ V65) binding
- T195 (= T121) binding
- Q197 (= Q123) binding
- V206 (≠ S132) binding
- R207 (= R133) binding ; binding
- H244 (= H170) binding
- R283 (= R211) binding
- S285 (= S213) binding
- G333 (≠ S262) binding
- E370 (= E302) binding
- A373 (≠ G305) binding
- G609 (= G533) binding
- H610 (= H534) binding axial binding residue
- D611 (≠ S535) binding
- R612 (≠ N536) binding
- S655 (= S579) binding
- L657 (= L581) binding
- G686 (= G610) binding
Sites not aligning to the query:
- 1 modified: Initiator methionine, Removed
- 75 binding
- 709 binding
5reqA Methylmalonyl-coa mutase, y89f mutant, substrate complex (see paper)
36% identity, 96% coverage: 4:631/655 of query aligns to 75:704/725 of 5reqA
- active site: F86 (≠ Y15), Y240 (= Y169), H241 (= H170), K601 (= K528), D605 (= D532), H607 (= H534)
- binding cobalamin: L116 (= L45), A136 (≠ V65), R204 (= R133), H241 (= H170), E244 (= E173), G330 (≠ S262), W331 (≠ L263), E367 (= E302), A368 (= A303), A370 (≠ G305), G606 (= G533), H607 (= H534), D608 (≠ S535), R609 (≠ N536), G610 (= G537), I614 (= I541), S652 (= S579), L654 (= L581), G682 (= G609), G683 (= G610), V684 (≠ I611), Y702 (= Y629), T703 (= T630)
- binding methylmalonyl(carbadethia)-coenzyme a: M75 (= M4), R79 (= R8), T82 (≠ L11), R84 (= R13), F86 (≠ Y15), S111 (= S40), S161 (= S90), T163 (= T92), T192 (= T121), Q194 (= Q123), R204 (= R133), N233 (= N162), H241 (= H170), R280 (= R211), S282 (= S213), F284 (= F215), T324 (≠ Y256), H325 (≠ G257), Q358 (≠ R293), S359 (≠ A294)
- binding succinyl(carbadethia)-coenzyme a: M75 (= M4), R79 (= R8), T82 (≠ L11), R84 (= R13), F86 (≠ Y15), S161 (= S90), T163 (= T92), T192 (= T121), R204 (= R133), N233 (= N162), H241 (= H170), R280 (= R211), S282 (= S213), F284 (= F215), H325 (≠ G257), Q358 (≠ R293)
Sites not aligning to the query:
1e1cA Methylmalonyl-coa mutase h244a mutant (see paper)
36% identity, 96% coverage: 4:631/655 of query aligns to 77:706/727 of 1e1cA
- active site: Y88 (= Y15), Y242 (= Y169), A243 (≠ H170), K603 (= K528), D607 (= D532), H609 (= H534)
- binding cobalamin: Y88 (= Y15), L118 (= L45), H121 (≠ Q48), A138 (≠ V65), V205 (≠ S132), R206 (= R133), E246 (= E173), G332 (≠ S262), W333 (≠ L263), E369 (= E302), A370 (= A303), A372 (≠ G305), L373 (= L306), G608 (= G533), H609 (= H534), D610 (≠ S535), R611 (≠ N536), G612 (= G537), I616 (= I541), Y620 (≠ A545), S654 (= S579), L656 (= L581), G684 (= G609), G685 (= G610), V686 (≠ I611), Y704 (= Y629), T705 (= T630)
- binding desulfo-coenzyme a: M77 (= M4), F80 (≠ D7), R81 (= R8), T84 (≠ L11), R86 (= R13), S113 (= S40), S163 (= S90), T165 (= T92), T194 (= T121), R282 (= R211), S284 (= S213), H327 (≠ G257), Q360 (≠ R293)
Sites not aligning to the query:
P22033 Methylmalonyl-CoA mutase, mitochondrial; MCM; Methylmalonyl-CoA isomerase; EC 5.4.99.2 from Homo sapiens (Human) (see 28 papers)
35% identity, 96% coverage: 2:631/655 of query aligns to 97:724/750 of P22033
- Y100 (≠ Q5) to C: in MMAM; mut-; no effect on protein abundance; decreased methylmalonyl-CoA mutase activity; decreased affinity for adenosylcob(III)alamin; alters thermodynamic stability; dbSNP:rs864309735
- W105 (= W10) to R: in MMAM; mut0; dbSNP:rs121918249
- TIRQY 106:110 (≠ LIRTY 11:15) binding
- R108 (= R13) to C: in MMAM; mut0; dbSNP:rs121918257; to G: in MMAM; mut-; to H: in MMAM; mut0; dbSNP:rs483352778
- Q109 (≠ T14) to R: in MMAM; mut0; dbSNP:rs1461110052
- G133 (= G38) to R: in MMAM; mut0; decreased protein abundance; decreased methylmalonyl-CoA mutase activity; dbSNP:rs879253828
- A137 (= A42) to V: in MMAM; mut0; dbSNP:rs941483851
- D139 (= D44) to N: in MMAM; uncertain significance; dbSNP:rs879253829
- L140 (= L45) to P: in MMAM; decreased protein expression; decreased methylmalonyl-CoA mutase activity
- A141 (≠ P46) to T: in MMAM; decreased protein expression; dbSNP:rs1554160730
- H143 (≠ Q48) to Y: in MMAM; mut0
- G145 (= G50) to S: in MMAM; mut0
- S148 (= S53) to L: in MMAM; mut0; dbSNP:rs1300547552
- D156 (≠ E61) to N: in MMAM; mut-
- G158 (= G63) to V: in MMAM; mut0
- G161 (= G66) to R: in MMAM; mut0; decreased protein abundance; decreased methylmalonyl-CoA mutase activity; to V: in MMAM; decreased protein expression
- F174 (= F79) to S: in MMAM; mut0; dbSNP:rs864309733
- M186 (= M91) to V: in MMAM; mut-; dbSNP:rs148331800
- T187 (= T92) to S: in MMAM; mut0; dbSNP:rs879253830
- N189 (= N94) to I: in MMAM; mut-; decreased protein abundance; decreased methylmalonyl-CoA mutase activity; dbSNP:rs200908035; to K: in MMAM; mut-; dbSNP:rs1561959114
- A191 (≠ T96) to E: in MMAM; mut- and mut0; affects proper folding; reduced protein level; decreased methylmalonyl-CoA mutase activity; dbSNP:rs760782399
- A197 (≠ S102) to E: in MMAM; mut0
- G203 (≠ A108) to R: in MMAM; mut0; decreased protein abundance; decreased methylmalonyl-CoA mutase activity; dbSNP:rs778702777
- E205 (= E110) natural variant: Missing (in MMAM; mut0; dbSNP:rs879253831)
- G215 (= G120) to C: in MMAM; mut- and mut0; dbSNP:rs121918258; to S: in MMAM; mut0; dbSNP:rs121918258
- TIQ 216:218 (≠ TVQ 121:123) binding
- Q218 (= Q123) to H: in MMAM; mut0 and mut-; no effect on protein abundance; loss of methylmalonyl-CoA mutase activity; alters thermodynamic stability; dbSNP:rs1446389693
- N219 (= N124) to Y: in MMAM; mut0; no effect on protein abundance; loss of methylmalonyl-CoA mutase activity; dbSNP:rs121918256
- R228 (= R133) binding ; to Q: in MMAM; mut0; dbSNP:rs770810987
- T230 (= T135) to I: in MMAM; mut-; to R: in MMAM; mut0; decreased protein abundance; decreased methylmalonyl-CoA mutase activity; dbSNP:rs879253833
- Y231 (= Y136) to N: in MMAM; mut-; no effect on protein abundance; decreased methylmalonyl-CoA mutase activity; strong decreased affinity for adenosylcob(III)alamin; alters thermodynamic stability; dbSNP:rs864309736
- K255 (= K160) binding
- S262 (≠ C167) to N: in MMAM; mut0
- H265 (= H170) binding ; to Y: in MMAM; mut-
- E276 (= E181) to D: in MMAM; uncertain significance; mut-; dbSNP:rs12175488
- L281 (= L186) to S: in MMAM; mut0; dbSNP:rs796052007
- G284 (≠ A189) to E: in MMAM; mut0; dbSNP:rs879253835; to R: in MMAM; mut0; dbSNP:rs761477436
- S288 (≠ V192) to P: in MMAM; mut0; decreased protein abundance; decreased methylmalonyl-CoA mutase activity; dbSNP:rs1179778233
- G291 (≠ E195) to E: in MMAM; mut0
- Q293 (≠ K197) to P: in MMAM; mut0
- RLS 304:306 (≠ RIS 211:213) binding
- L305 (≠ I212) to S: in MMAM; mut0; decreased protein abundance; decreased methylmalonyl-CoA mutase activity; dbSNP:rs1554160246
- S306 (= S213) to F: in MMAM; mut0; dbSNP:rs1085307929
- W309 (≠ V216) to G: in MMAM; decreased protein expression
- G312 (= G219) to V: in MMAM; mut0; dbSNP:rs864309734
- Y316 (≠ V223) to C: in MMAM; mut-; no effect on protein abundance; decreased methylmalonyl-CoA mutase activity; no decreased affinity for adenosylcob(III)alamin; dbSNP:rs781474200
- A324 (= A231) to T: in MMAM; mut-; dbSNP:rs780387525
- R326 (≠ V233) to K: in MMAM; uncertain significance; dbSNP:rs758577372
- L328 (= L235) to F: in MMAM; mut0; affects proper folding; no effect on protein abundance; loss of methylmalonyl-CoA mutase activity; dbSNP:rs796052002; to P: in MMAM; mut0; dbSNP:rs965316043
- S344 (≠ F251) to F: in MMAM; mut-; affects proper folding; no effect on protein abundance; loss of methylmalonyl-CoA mutase activity; decreased affinity for adenosylcob(III)alamin
- L346 (≠ R253) natural variant: Missing (in MMAM; mut0)
- L347 (≠ F254) to R: in MMAM; mut0; dbSNP:rs1026703654
- H350 (≠ G257) to Y: in MMAM; mut0; dbSNP:rs1407914109
- L358 (= L265) to P: in MMAM; mut0
- N366 (= N273) to S: in MMAM; mut-; no effect on protein abundance; loss of methylmalonyl-CoA mutase activity; decreased affinity for adenosylcob(III)alamin; alters thermodynamic stability; dbSNP:rs864309737
- R369 (= R276) to C: in MMAM; mut0; dbSNP:rs772552898; to H: in MMAM; mut- and mut0; no effect on protein abundance; loss of methylmalonyl-CoA mutase activity; alters thermodynamic stability; dbSNP:rs564069299
- T370 (≠ I277) to P: in MMAM; mut0; dbSNP:rs368790885
- A377 (≠ V284) to E: in MMAM; mut0; decreased protein abundance; decreased methylmalonyl-CoA mutase activity; dbSNP:rs121918250
- Q383 (≠ R293) to H: in MMAM; mut0; to P: in MMAM; mut0
- H386 (≠ Q296) to N: in MMAM; mut0; dbSNP:rs1554159937; to R: in MMAM; mut0; dbSNP:rs866933356
- T387 (≠ L297) to I: in MMAM; mut-; no effect on protein abundance; decreased methylmalonyl-CoA mutase activity; decreased affinity for adenosylcob(III)alamin; alters thermodynamic stability
- N388 (≠ P298) to H: in MMAM; mut0; dbSNP:rs766010704; to K: in MMAM; mut0; decreased protein abundance; decreased methylmalonyl-CoA mutase activity; dbSNP:rs879253840
- S389 (≠ A299) natural variant: Missing (in MMAM; mut0)
- I412 (≠ L322) natural variant: Missing (in MMAM; mut0)
- P424 (≠ L334) to L: in MMAM; mut0; decreased protein abundance; decreased methylmalonyl-CoA mutase activity; dbSNP:rs879253842
- G426 (≠ D336) to E: in MMAM; mut-; decreased protein abundance; decreased methylmalonyl-CoA mutase activity; dbSNP:rs533755473; to R: in MMAM; mut-; no effect on protein abundance; decreased methylmalonyl-CoA mutase activity; strong decreased affinity for adenosylcob(III)alamin; alters thermodynamic stability; dbSNP:rs769922244
- G427 (= G337) to D: in MMAM; mut0; dbSNP:rs753288303
- G454 (= G364) to E: in MMAM; mut0
- A499 (≠ G413) to T: in dbSNP:rs2229385
- I505 (≠ V418) to T: in MMAM; decreased protein expression; decreased methylmalonyl-CoA mutase activity
- Q514 (= Q426) to E: in MMAM; uncertain significance; to K: in MMAM; decreased protein expression
- L518 (= L430) to P: in MMAM; mut0; dbSNP:rs864309738
- R532 (≠ S444) to H: in dbSNP:rs1141321
- A535 (= A447) to P: in MMAM; mut0; dbSNP:rs760183775
- A552 (≠ S463) to V: in MMAM; uncertain significance; dbSNP:rs879253845
- C560 (≠ V471) to Y: in MMAM; mut0; dbSNP:rs1238333040
- T566 (≠ A477) to R: in MMAM; mut0
- F573 (≠ Y484) to S: in MMAM; mut-; affects proper folding; no effect on protein abundance; no effect on methylmalonyl-CoA mutase activity; decreased affinity for adenosylcob(III)alamin; does not alter thermodynamic stability; dbSNP:rs775593146
- Y587 (≠ S494) to C: in MMAM; mut-
- I597 (≠ L504) to R: in MMAM; no changed in protein expression; decreased methylmalonyl-CoA mutase activity; dbSNP:rs1554158951
- P615 (≠ L522) to L: in MMAM; mut0; affects proper folding; reduced strongly protein level; to R: in MMAM; mut0; dbSNP:rs1554158777; to T: in MMAM; mut0; affects proper folding; reduced strongly protein level; loss of methylmalonyl-CoA mutase activity; dbSNP:rs1302409621
- R616 (≠ K523) to C: in MMAM; mut0; dbSNP:rs765284825
- L617 (≠ F524) to R: in MMAM; mut0; dbSNP:rs1554158775
- K621 (= K528) to N: in MMAM; mut0
- G623 (= G530) to R: in MMAM; mut0; dbSNP:rs121918254
- Q624 (≠ L531) to R: in MMAM; no effect on protein abundance; dbSNP:rs768521956
- D625 (= D532) to G: in MMAM; mut0; decreased protein abundance; decreased methylmalonyl-CoA mutase activity; dbSNP:rs879253847; to V: in MMAM; mut0; no effect on protein abundance; decreased methylmalonyl-CoA mutase activity
- G626 (= G533) to C: in MMAM; mut-; dbSNP:rs982110849
- H627 (= H534) binding axial binding residue; to R: in MMAM; mut0; dbSNP:rs372486357
- G630 (= G537) to E: in MMAM; mut0; dbSNP:rs143023066
- V633 (≠ Q540) to G: in MMAM; mut-; no effect on protein abundance; decreased methylmalonyl-CoA mutase activity; decreased affinity for adenosylcob(III)alamin; does not alter thermodynamic stability; dbSNP:rs200055428
- G637 (≠ R544) to E: in MMAM; mut-; to R: in MMAM; mut0; dbSNP:rs781501004
- F638 (≠ A545) to I: in MMAM; mut0
- D640 (= D547) to Y: in MMAM; mut0; dbSNP:rs865815395
- G642 (= G549) to R: in MMAM; mut-; dbSNP:rs747897332
- G648 (≠ D555) to D: in MMAM; mut-; no effect on protein abundance; decreased methylmalonyl-CoA mutase activity; strong decreased affinity for adenosylcob(III)alamin; alters thermodynamic stability; dbSNP:rs766721811
- V669 (= V576) to E: in MMAM; mut0; dbSNP:rs1360470463
- I671 (≠ M578) to V: in dbSNP:rs8589
- L674 (= L581) to F: in MMAM; decreased protein abundance; decreased methylmalonyl-CoA mutase activity; dbSNP:rs1164271240
- H678 (= H585) to R: in MMAM; mut-; dbSNP:rs147094927
- E684 (= E591) natural variant: E -> EL (in MMAM; mut-)
- L685 (= L592) to R: in MMAM; mut-; dbSNP:rs864309739
- R694 (≠ L601) to L: in MMAM; mut-; decreased protein abundance; loss of methylmalonyl-CoA mutase activity; decreased affinity for adenosylcob(III)alamin; alters thermodynamic stability; to W: in MMAM; mut- and mut0; no effect on protein abundance; loss of methylmalonyl-CoA mutase activity; decreased affinity for adenosylcob(III)alamin; alters thermodynamic stability; dbSNP:rs777758903
- M700 (≠ I607) to K: in MMAM; mut-; no effect on protein abundance; loss of methylmalonyl-CoA mutase activity; decreased affinity for adenosylcob(III)alamin; alters thermodynamic stability; dbSNP:rs140600746
- G703 (= G610) to R: in MMAM; mut0; dbSNP:rs121918255
- G717 (= G624) to V: in MMAM; mut-; no effect on protein abundance; interferes with the binding of the cofactor to the apoenzyme; decreased methylmalonyl-CoA mutase activity; strong decreased affinity for adenosylcob(III)alamin; decreased thermodynamic stability; dbSNP:rs121918252
- G723 (≠ T630) to D: in MMAM; decreased protein expression; decreased methylmalonyl-CoA mutase activity; dbSNP:rs755077681
Sites not aligning to the query:
- 1:32 modified: transit peptide, Mitochondrion
- 7:750 natural variant: Missing (in MMAM; mut-)
- 50 binding
- 69 I → V: in MMAM; likely benign; dbSNP:rs115923556
- 86 P → L: in MMAM; mut0 and mut-; no effect on protein abundance; decreased methylmalonyl-CoA mutase activity; decreased affinity for adenosylcob(III)alamin; alters thermodynamic stability; dbSNP:rs769348060
- 87 G → E: in MMAM; mut0; dbSNP:rs1554160986
- 93 R → H: in MMAM; mut0; decreased methylmalonyl-CoA mutase activity; dbSNP:rs121918251
- 94 G → R: in MMAM; mut0; dbSNP:rs727504022; G → V: in MMAM; mut- and mut0; dbSNP:rs535411418
- 95 P → R: in MMAM; mut0; dbSNP:rs190834116
- 96:99 binding
- 152:750 natural variant: Missing (in MMAM; mut0)
- 228:750 natural variant: Missing (in MMAM; mut0)
2xiqA Crystal structure of human methylmalonyl-coa mutase in complex with adenosylcobalamin and malonyl-coa (see paper)
35% identity, 96% coverage: 2:631/655 of query aligns to 62:689/714 of 2xiqA
- active site: Y75 (= Y15), Y229 (= Y169), H230 (= H170), K586 (= K528), D590 (= D532), H592 (= H534)
- binding cobalamin: Y75 (= Y15), L105 (= L45), H108 (≠ Q48), A125 (≠ V65), R193 (= R133), E233 (= E173), G320 (≠ S262), W321 (≠ L263), E357 (= E302), G360 (= G305), L361 (= L306), G591 (= G533), H592 (= H534), D593 (≠ S535), R594 (≠ N536), G595 (= G537), I599 (= I541), G635 (= G577), S637 (= S579), L639 (= L581), A641 (≠ G583), G667 (= G609), G668 (= G610), F687 (≠ Y629), G688 (≠ T630)
- binding malonyl-coenzyme a: T63 (≠ Q3), M64 (= M4), R68 (= R8), T71 (≠ L11), R73 (= R13), Y75 (= Y15), S150 (= S90), T152 (= T92), T181 (= T121), R193 (= R133), K220 (= K160), H230 (= H170), R269 (= R211), S271 (= S213), F273 (= F215), R313 (= R255), A314 (≠ Y256), H315 (≠ G257), Q317 (= Q259), Q348 (≠ R293)
Sites not aligning to the query:
8dyjB Crystal structure of human methylmalonyl-coa mutase in complex with adp and cob(ii)alamin (see paper)
35% identity, 96% coverage: 2:631/655 of query aligns to 61:688/708 of 8dyjB
- binding adenosine-5'-diphosphate: Y74 (= Y15), T151 (= T92), R192 (= R133), Y228 (= Y169), H229 (= H170), F272 (= F215), Q316 (= Q259), N352 (≠ P298), E356 (= E302), L360 (= L306), P361 (= P307)
- binding cobalamin: F102 (= F43), L104 (= L45), H107 (≠ Q48), A124 (≠ V65), V191 (≠ S132), R192 (= R133), H229 (= H170), E232 (= E173), G319 (≠ S262), W320 (≠ L263), E356 (= E302), G359 (= G305), L360 (= L306), G590 (= G533), H591 (= H534), D592 (≠ S535), R593 (≠ N536), G594 (= G537), I598 (= I541), S636 (= S579), L638 (= L581), A640 (≠ G583), G666 (= G609), G667 (= G610), V668 (≠ I611), F686 (≠ Y629), G687 (≠ T630)
Sites not aligning to the query:
8gjuJ Crystal structure of human methylmalonyl-coa mutase (mmut) in complex with methylmalonic acidemia type a protein (mmaa), coenzyme a, and gdp (see paper)
35% identity, 96% coverage: 2:631/655 of query aligns to 62:666/689 of 8gjuJ
- binding coenzyme a: T63 (≠ Q3), R68 (= R8), T71 (≠ L11), R73 (= R13), S150 (= S90), T152 (= T92), T181 (= T121), Q183 (= Q123), N222 (= N162), R269 (= R211), S271 (= S213), R313 (= R255), A314 (≠ Y256), H315 (≠ G257), Q348 (≠ R293)
Sites not aligning to the query:
4r3uA Crystal structure of 2-hydroxyisobutyryl-coa mutase (see paper)
34% identity, 74% coverage: 2:488/655 of query aligns to 76:556/557 of 4r3uA
- active site: I89 (≠ Y15), Y243 (= Y169), H244 (= H170)
- binding 3-hydroxybutanoyl-coenzyme a: T77 (≠ Q3), M78 (= M4), R82 (= R8), T85 (≠ L11), R87 (= R13), I89 (≠ Y15), D116 (≠ A42), S164 (= S90), T166 (= T92), T195 (= T121), Q197 (= Q123), R234 (≠ K160), N236 (= N162), N239 (= N165), Y243 (= Y169), H244 (= H170), R283 (= R211), F287 (= F215), R327 (= R255), F328 (≠ Y256), H329 (≠ G257), Q331 (= Q259), Q362 (≠ R293)
- binding S-{(3R,5R,9R)-1-[(2R,3S,4R,5R)-5-(6-amino-9H-purin-9-yl)-4-hydroxy-3-(phosphonooxy)tetrahydrofuran-2-yl]-3,5,9-trihydroxy-8,8-dimethyl-3,5-dioxido-10,14-dioxo-2,4,6-trioxa-11,15-diaza-3lambda~5~,5lambda~5~-diphosphaheptadecan-17-yl} 2-hydroxy-2-methylpropanethioate: T77 (≠ Q3), M78 (= M4), R82 (= R8), T85 (≠ L11), R87 (= R13), I89 (≠ Y15), D116 (≠ A42), S164 (= S90), T166 (= T92), T195 (= T121), Q197 (= Q123), R234 (≠ K160), N236 (= N162), N239 (= N165), H244 (= H170), R283 (= R211), F287 (= F215), R327 (= R255), F328 (≠ Y256), H329 (≠ G257), Q331 (= Q259), Q362 (≠ R293)
- binding cobalamin: D116 (≠ A42), M119 (≠ L45), E139 (≠ V65), Q207 (≠ R133), E209 (≠ T135), E247 (= E173), A334 (≠ S262), E371 (= E302), A372 (= A303), A374 (≠ G305)
Sites not aligning to the query:
- binding 3-hydroxybutanoyl-coenzyme a: 75
- binding S-{(3R,5R,9R)-1-[(2R,3S,4R,5R)-5-(6-amino-9H-purin-9-yl)-4-hydroxy-3-(phosphonooxy)tetrahydrofuran-2-yl]-3,5,9-trihydroxy-8,8-dimethyl-3,5-dioxido-10,14-dioxo-2,4,6-trioxa-11,15-diaza-3lambda~5~,5lambda~5~-diphosphaheptadecan-17-yl} 2-hydroxy-2-methylpropanethioate: 75
I3VE77 2-hydroxyisobutanoyl-CoA mutase large subunit; 2-hydroxyisobutyryl-CoA mutase large subunit; HCM large subunit; EC 5.4.99.64 from Aquincola tertiaricarbonis (see 2 papers)
34% identity, 74% coverage: 2:488/655 of query aligns to 77:557/562 of I3VE77
- TMR 86:88 (≠ LIR 11:13) binding
- I90 (≠ Y15) mutation to A: 6-fold decrease in catalytic efficiency with 2-hydroxyisobutyryl-CoA as substrate. 320-fold decrease in catalytic efficiency with (S)-3-hydroxybuytryl-CoA as substrate. 6-fold increase in catalytic efficiency with (R)-3-hydroxybutyryl-CoA as substrate. No change in catalytic efficiencies with pivalyl-CoA and isovaleryl-CoA as substrates.; mutation I->F,Y: Loss of activity.; mutation to L: 37-fold decrease in catalytic efficiency with 2-hydroxyisobutyryl-CoA as substrate. 290-fold decrease in catalytic efficiency with (S)-3-hydroxybuytryl-CoA as substrate. Does not show any significant activities with pivalyl-CoA and isovaleryl-CoA.; mutation to V: 100-fold decrease in catalytic efficiency with (S)-3-hydroxybuytryl-CoA as substrate. No change in catalytic efficiencies with pivalyl-CoA and isovaleryl-CoA as substrates.
- D117 (≠ A42) binding ; mutation to A: 2-fold increase in catalytic efficiency with 2-hydroxyisobutyryl-CoA as substrate. Small increase in catalytic efficiency with (S)-3-hydroxybuytryl-CoA as substrate. 1800-fold increase in catalytic efficiency with (R)-3-hydroxybutyryl-CoA as substrate.; mutation to V: 1.5-fold increase in catalytic efficiency with 2-hydroxyisobutyryl-CoA as substrate. 3-fold decrease in catalytic efficiency with (S)-3-hydroxybuytryl-CoA as substrate. 1300-fold increase in catalytic efficiency with (R)-3-hydroxybutyryl-CoA as substrate. 74-fold increase in catalytic efficiency with pivalyl-CoA as substrate.
- TVQ 196:198 (= TVQ 121:123) binding
- R235 (≠ K160) binding
- N240 (= N165) binding
- H245 (= H170) binding
- R284 (= R211) binding
Sites not aligning to the query:
Q5KUG0 Fused isobutyryl-CoA mutase; EC 5.4.99.13; EC 3.6.5.- from Geobacillus kaustophilus (strain HTA426) (see paper)
25% identity, 73% coverage: 13:488/655 of query aligns to 587:1083/1086 of Q5KUG0
Sites not aligning to the query:
- 213 K→A: Loss of GTPase and ATPase activities. No effect on the mutase activity.
4xc7A Isobutyryl-coa mutase fused with bound butyryl-coa and without cobalamin or gdp (apo-icmf) (see paper)
24% identity, 73% coverage: 13:488/655 of query aligns to 564:1050/1053 of 4xc7A
- active site: F566 (≠ Y15), Y747 (= Y169), H748 (= H170)
- binding Butyryl Coenzyme A: R564 (= R13), F566 (≠ Y15), R590 (vs. gap), S645 (vs. gap), T647 (= T92), R696 (≠ Q119), T698 (= T121), Y740 (≠ N162), S789 (= S213), F791 (= F215), R824 (≠ K250), K829 (≠ R255), H831 (≠ G257)
Sites not aligning to the query:
4xc6A Isobutyryl-coa mutase fused with bound adenosylcobalamin, gdp, and mg (holo-icmf/gdp) (see paper)
24% identity, 73% coverage: 13:488/655 of query aligns to 570:1064/1067 of 4xc6A
- active site: F572 (≠ Y15), Y753 (= Y169), H754 (= H170)
- binding cobalamin: F601 (= F43), L606 (≠ Q48), S624 (≠ V65), Q716 (≠ R133), H754 (= H170), E757 (= E173), A758 (= A174), G842 (≠ S262), R843 (≠ L263), E879 (= E302), A880 (= A303), T882 (≠ G305), H967 (≠ K389)
- binding guanosine-5'-diphosphate: E947 (= E370)
Sites not aligning to the query:
- active site: 6
- binding cobalamin: 18, 19, 20, 21, 22, 26, 66, 67, 94, 96, 98, 116, 117, 118, 129
- binding guanosine-5'-diphosphate: 199, 201, 202, 203, 204, 245, 337, 338, 340, 375, 377
- binding magnesium ion: 203, 229, 242, 242, 290, 290
Q1LRY0 Fused isobutyryl-CoA mutase; EC 5.4.99.13; EC 3.6.5.- from Cupriavidus metallidurans (strain ATCC 43123 / DSM 2839 / NBRC 102507 / CH34) (Ralstonia metallidurans) (see 2 papers)
24% identity, 73% coverage: 13:488/655 of query aligns to 596:1090/1093 of Q1LRY0
- F598 (≠ Y15) mutation to A: Switches the substrate specificity and enhances the catalytic efficiency of the isovaleryl-CoA mutase over the native isobutyryl-CoA mutase activity about 4000-fold. Is even more susceptible to inactivation than wild-type during turnover.
- R622 (vs. gap) binding
- R728 (≠ Q119) binding
- Y772 (≠ N162) binding
- S821 (= S213) binding
- R856 (≠ K250) binding
- K861 (≠ R255) binding
- E973 (= E370) binding
Sites not aligning to the query:
- 39 binding axial binding residue
- 169:417 GTPase chaperone MeaI
- 219:224 binding
- 223 binding
- 248 binding
- 249 binding
- 262 binding ; binding
- 265 binding
- 310 binding ; binding
- 311 binding
- 357:360 binding
- 418:579 Linker
- 587 binding
- 1092 binding
5cjtA Isobutyryl-coa mutase fused with bound adenosylcobalamin, gdp, mg (holo-icmf/gdp), and substrate isobutyryl-coenzyme a (see paper)
24% identity, 73% coverage: 13:488/655 of query aligns to 567:1059/1062 of 5cjtA
- active site: F569 (≠ Y15), Y750 (= Y169), H751 (= H170)
- binding cobalamin: F598 (= F43), L603 (≠ Q48), S621 (≠ V65), Q713 (≠ R133), H751 (= H170), E754 (= E173), A755 (= A174), G839 (≠ S262), R840 (≠ L263), E876 (= E302), A877 (= A303), T879 (≠ G305), H964 (≠ K389)
- binding isobutyryl-coenzyme a: R567 (= R13), F569 (≠ Y15), R593 (vs. gap), S648 (vs. gap), T650 (= T92), R699 (≠ Q119), T701 (= T121), Q703 (= Q123), Y743 (≠ N162), Y750 (= Y169), H751 (= H170), S792 (= S213), F794 (= F215), R827 (≠ K250), K832 (≠ R255), H834 (≠ G257)
- binding guanosine-5'-diphosphate: E944 (= E370)
Sites not aligning to the query:
- active site: 6
- binding cobalamin: 18, 19, 20, 21, 22, 26, 66, 67, 94, 96, 98, 116, 117
- binding isobutyryl-coenzyme a: 556, 558, 560
- binding guanosine-5'-diphosphate: 199, 201, 202, 203, 204, 245, 336, 337, 339, 374, 376
- binding magnesium ion: 203, 229, 242, 242, 289, 289
Query Sequence
>GFF373 PGA1_c03840 methylmalonyl-CoA mutase large subunit
MPQMQKDRPWLIRTYAGHSTASASNALYRANLAKGQTGLSVAFDLPTQTGYDSDHVLARG
EVGKVGVPVCHLGDMRSLFDQIPLEQMNTSMTINATAPWLLSLYIAVAEEQGADVSKLQG
TVQNDLIKEYLSRGTYVCPPKPSLKMIADVAEYCYTNAPKWNPMNVCSYHLQEAGATPEQ
ELAFALATAQAVLDELKPRITPEDFPAMVGRISFFVNAGIRFVTEMCKMRAFVDLWDEIC
RDRYGVEDPKFRRFRYGVQVNSLGLTEQQPENNVYRILIEMLAVTLSKKARARAVQLPAW
NEALGLPRPWDQQWSMRMQQILAYETDLLEYGDLFDGNPAVDAKVEDLKTGARAELANLE
SMGGAVASIEYMKGRLVDSNAERLNRIEKNETIVVGVNKWTEGEPSPLQTEDGGIMVVDP
AVEQEQINRLDDWRSGRDDDAVQSALAALRAAAQNGDNIMPPSIAAAKAGVTTGEWAEEM
RKVYGTYRGPTGVSGSASNKTEGLDELRDKVNAVSDQLGRRLKFLVGKPGLDGHSNGAEQ
IAFRARDCGMDITYDGIRMTPEELVASAIADDAHVVGMSILSGSHLPLIEELMGRMTEAG
LSHVPVIVGGIIPDDDADRLKKMGVARVYTPKDFELNAIMGDIVELAKQPETATH
Or try a new SitesBLAST search
SitesBLAST's Database
SitesBLAST's database includes
(1) SwissProt
entries with experimentally-supported functional features;
and (2) protein structures with bound ligands, from the
BioLip database.
by Morgan Price,
Arkin group
Lawrence Berkeley National Laboratory