SitesBLAST
Comparing RR42_RS13255 FitnessBrowser__Cup4G11:RR42_RS13255 to proteins with known functional sites using BLASTp with E ≤ 0.001.
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Found 20 (the maximum) hits to proteins with known functional sites (download)
6ndsA Structure of an hmg-coa lyase from acenitobacter baumannii in complex with coenzyme a and 3-methylmalate
50% identity, 92% coverage: 15:311/322 of query aligns to 10:305/305 of 6ndsA
- binding coenzyme a: V52 (≠ T57), S53 (= S58), I57 (= I62), N84 (= N89), G87 (= G92), R90 (= R95), N113 (= N118), M114 (≠ L119), R115 (= R120)
- binding zinc ion: D17 (= D22), H207 (= H213), H209 (= H215)
Q8TB92 3-hydroxy-3-methylglutaryl-CoA lyase, cytoplasmic; 3-hydroxy-3-methylglutaryl-CoA lyase-like protein 1; HMGCL-like 1; Endoplasmic reticulum 3-hydroxy-3-methylglutaryl-CoA lyase; er-cHL; EC 4.1.3.4 from Homo sapiens (Human) (see 2 papers)
36% identity, 93% coverage: 4:301/322 of query aligns to 68:366/370 of Q8TB92
- R86 (= R21) mutation to Q: Abolishes catalytic activity.
- L237 (≠ F172) mutation to S: Abolishes catalytic activity.
- H278 (= H213) mutation to R: Abolishes catalytic activity.
Sites not aligning to the query:
- 2 modified: N-myristoyl glycine; G→A: Abolishes myristoylation and induces a subcellular location change.
P35914 Hydroxymethylglutaryl-CoA lyase, mitochondrial; HL; HMG-CoA lyase; 3-hydroxy-3-methylglutarate-CoA lyase; EC 4.1.3.4 from Homo sapiens (Human) (see 11 papers)
37% identity, 95% coverage: 1:305/322 of query aligns to 21:325/325 of P35914
- E37 (= E17) to K: in HMGCLD; activity lower than 5% respect to the wild-type; mutation to D: Normal activity.
- R41 (= R21) to Q: in HMGCLD; loss of activity and of proton exchange; dbSNP:rs121964997; mutation to M: Reduced activity, and loss of proton exchange.
- D42 (= D22) to E: in HMGCLD; reduced activity; to G: in HMGCLD; loss of activity; dbSNP:rs1467902610; to H: in HMGCLD; loss of activity; mutation D->A,N: Loss of activity, and reduced proton exchange rate.
- K48 (≠ P28) to N: in HMGCLD; abolishes almost all enzymatic activity
- E72 (= E52) mutation to A: Loss of activity, and reduced affinity for metal cofactor and substrate.
- S142 (≠ T122) to F: in HMGCLD; activity lower than 5% respect to the wild-type
- C174 (= C154) to Y: in HMGCLD; activity lower than 5% respect to the wild-type; dbSNP:rs765475941
- F192 (= F172) to S: in HMGCLD; activity lower than 5% respect to the wild-type
- I200 (= I180) to F: in HMGCLD; activity lower than 5% respect to the wild-type
- G203 (≠ C183) to E: in HMGCLD; complete loss of activity; dbSNP:rs1553131940
- D204 (= D184) mutation to A: Reduced activity, and reduced affinity for metal cofactor and substrate.
- H233 (= H213) to R: in HMGCLD; loss of activity; dbSNP:rs727503963; mutation to A: Loss of activity, and reduced proton exchange rate.
- E279 (= E259) mutation to A: Reduced thermal stability, but normal activity.
- D280 (≠ E260) mutation to A: Normal activity.
- C323 (≠ T303) modified: Interchain; mutation to S: Abolishes interchain homodimerization. Exhibits no DTT stimulated activity.
3mp3B Crystal structure of human lyase in complex with inhibitor hg-coa (see paper)
37% identity, 91% coverage: 10:301/322 of query aligns to 3:294/296 of 3mp3B
- binding (3R,5S,9R,21S)-1-[(2R,3S,4R,5R)-5-(6-amino-9H-purin-9-yl)-4-hydroxy-3-(phosphonooxy)tetrahydrofuran-2-yl]-3,5,9,21-tetrahydroxy-8,8-dimethyl-10,14,19-trioxo-2,4,6-trioxa-18-thia-11,15-diaza-3,5-diphosphatricosan-23-oic acid 3,5-dioxide: R14 (= R21), D15 (= D22), Q18 (= Q25), F49 (= F56), V50 (≠ T57), S51 (= S58), W54 (≠ A61), P81 (= P88), N82 (= N89), K84 (≠ R91), G85 (= G92), N111 (= N118), R122 (≠ Q129), Y140 (≠ S147), S142 (= S149), T178 (= T185), H206 (= H213)
- binding magnesium ion: D15 (= D22), H206 (= H213), H208 (= H215)
2cw6A Crystal structure of human hmg-coa lyase: insights into catalysis and the molecular basis for hydroxymethylglutaric aciduria (see paper)
37% identity, 91% coverage: 10:301/322 of query aligns to 3:294/296 of 2cw6A
1ydnA Crystal structure of the hmg-coa lyase from brucella melitensis, northeast structural genomics target lr35. (see paper)
44% identity, 83% coverage: 13:279/322 of query aligns to 4:270/283 of 1ydnA
3mp5B Crystal structure of human lyase r41m in complex with hmg-coa (see paper)
37% identity, 91% coverage: 10:301/322 of query aligns to 3:294/296 of 3mp5B
- binding 3-hydroxy-3-methylglutaryl-coenzyme a: D15 (= D22), Q18 (= Q25), S51 (= S58), W54 (≠ A61), F100 (≠ V107), N111 (= N118), N113 (≠ R120), Y140 (≠ S147), S142 (= S149), T178 (= T185), C239 (= C246)
- binding magnesium ion: D15 (= D22), H206 (= H213), H208 (= H215)
P13703 Hydroxymethylglutaryl-CoA lyase; HL; HMG-CoA lyase; 3-hydroxy-3-methylglutarate-CoA lyase; EC 4.1.3.4 from Pseudomonas mevalonii (see paper)
40% identity, 82% coverage: 13:276/322 of query aligns to 4:267/301 of P13703
- C237 (= C246) active site
6ktqA Crystal structure of catalytic domain of homocitrate synthase from sulfolobus acidocaldarius (sahcs(dram)) in complex with alpha- ketoglutarate/zn2+/coa (see paper)
27% identity, 70% coverage: 21:244/322 of query aligns to 30:247/399 of 6ktqA
- binding 2-oxoglutaric acid: R30 (= R21), R154 (≠ N145), T156 (≠ G153), E158 (≠ P155), S184 (≠ T181), T188 (= T185), H216 (= H213), H218 (= H215)
- binding coenzyme a: V67 (≠ S58), R96 (= R91), A97 (≠ G92), F116 (≠ V107), H128 (≠ L119), E158 (≠ P155)
- binding zinc ion: E31 (≠ D22), H216 (= H213), H218 (= H215)
3rmjB Crystal structure of truncated alpha-isopropylmalate synthase from neisseria meningitidis (see paper)
24% identity, 86% coverage: 12:287/322 of query aligns to 3:279/308 of 3rmjB
Q9JZG1 2-isopropylmalate synthase; Alpha-IPM synthase; Alpha-isopropylmalate synthase; EC 2.3.3.13 from Neisseria meningitidis serogroup B (strain MC58) (see 2 papers)
24% identity, 86% coverage: 12:287/322 of query aligns to 6:282/517 of Q9JZG1
- D16 (= D22) binding
- H204 (= H213) binding
- H206 (= H215) binding
- N240 (= N255) binding
Sites not aligning to the query:
- 366:517 Required for the condensation reaction. Not required to bind substrate
6e1jA Crystal structure of methylthioalkylmalate synthase (bjumam1.1) from brassica juncea (see paper)
26% identity, 53% coverage: 100:269/322 of query aligns to 115:275/409 of 6e1jA
Sites not aligning to the query:
- binding coenzyme a: 30, 60, 63, 95, 97, 322, 323, 324, 327, 331, 359, 362, 363
- binding manganese (ii) ion: 27, 82, 84
Q8F3Q1 (R)-citramalate synthase CimA; LiCMS; EC 2.3.3.21 from Leptospira interrogans serogroup Icterohaemorrhagiae serovar Lai (strain 56601) (see 2 papers)
25% identity, 87% coverage: 6:285/322 of query aligns to 1:280/516 of Q8F3Q1
- R16 (= R21) mutation R->K,Q: Loss of activity.
- RD 16:17 (= RD 21:22) binding
- D17 (= D22) mutation to A: 34-fold increase in Km for pyruvate and 315-fold decrease in kcat.; mutation to N: 4.4-fold increase in Km for pyruvate and 480-fold decrease in kcat.
- L81 (= L90) mutation to A: 4.7-fold increase in Km for pyruvate and 15.7-fold decrease in kcat.; mutation to V: 3.3-fold increase in Km for pyruvate and 10.1-fold decrease in kcat.
- F83 (≠ G92) mutation to A: 5-fold increase in Km for acetyl-CoA and 120-fold decrease in kcat.
- L104 (≠ V107) mutation to V: 1.8-fold increase in Km for pyruvate and 3.4-fold decrease in kcat.
- Y144 (≠ S147) binding ; mutation to L: 259-fold increase in Km for pyruvate and 76-fold decrease in kcat.; mutation to V: 114-fold increase in Km for pyruvate and 5.3-fold decrease in kcat.
- E146 (≠ S149) mutation E->D,Q: Minor effects on the binding of acetyl-CoA, but causes a strong decrease in kcat.
- T179 (= T185) binding ; mutation to A: 16.4-fold increase in Km for pyruvate and 186-fold decrease in kcat.
Sites not aligning to the query:
- 302 mutation H->A,N: Loss of activity.
- 304 D→A: 5.2-fold increase in Km for acetyl-CoA and 16.6-fold decrease in kcat.
- 310 N→A: 2.2-fold increase in Km for acetyl-CoA and 1.7-fold decrease in kcat.
- 311 L→A: 8-fold increase in Km for acetyl-CoA and 6-fold decrease in kcat.
- 312 Y→A: Loss of activity.
- 430 Y→L: No change in Km for acetyl-CoA and 2.3-fold decrease in kcat. Severely impairs inhibition by isoleucine.
- 431 D→A: 1.8-fold decrease in Km for acetyl-CoA and 5-fold decrease in kcat.
- 451 L→V: 1.5-fold increase in Km for acetyl-CoA and 4.3 decrease in kcat.
- 454 Y→A: 1.4 decrease in Km for acetyl-CoA and 17-fold decrease in kcat. Still inhibited by isoleucine and weakly inhibited by leucine.
- 458 I→A: 1.3-fold decrease in Km for acetyl-CoA and 14-fold decrease in kcat. Abolishes inhibition by isoleucine.
- 464 T→A: 1.8-fold decrease in Km for acetyl-CoA and 4.3-fold decrease in kcat.
- 468 V→A: No change in Km for acetyl-CoA and 2-fold decrease in kcat. Increases inhibition by isoleucine and leucine becomes an effective inhibitor.
- 493 P→A: 1.5-fold decrease in Km for acetyl-CoA and 2.6-fold decrease in kcat.
- 495 Q→A: 1.6-fold decrease in Km for acetyl-CoA and 2.8-fold decrease in kcat.
3bliA Crystal structure of the catalytic domain of licms in complexed with pyruvate and acetyl-coa (see paper)
25% identity, 85% coverage: 12:285/322 of query aligns to 1:274/311 of 3bliA
Q9FG67 Methylthioalkylmalate synthase 1, chloroplastic; 2-isopropylmalate synthase 3; EC 2.3.3.17 from Arabidopsis thaliana (Mouse-ear cress) (see paper)
24% identity, 50% coverage: 109:269/322 of query aligns to 190:342/506 of Q9FG67
- A290 (≠ T211) mutation to T: In gsm1-2; loss of conversion of C3 to C4 glucosinolates.
Sites not aligning to the query:
- 102 S→F: In gsm1-1; loss of conversion of C3 to C4 glucosinolates.
3mi3A Homocitrate synthase lys4 bound to lysine (see paper)
25% identity, 75% coverage: 2:244/322 of query aligns to 1:221/370 of 3mi3A
Q9FN52 Methylthioalkylmalate synthase 3, chloroplastic; 2-isopropylmalate synthase 2; Methylthioalkylmalate synthase-like; EC 2.3.3.17 from Arabidopsis thaliana (Mouse-ear cress) (see paper)
25% identity, 51% coverage: 106:269/322 of query aligns to 187:342/503 of Q9FN52
- G263 (= G187) mutation to E: In gsm2-1; loss of activity and lack of C6, C7 and C8 aliphatic glucosinolates.
3ivtB Homocitrate synthase lys4 bound to 2-og (see paper)
24% identity, 75% coverage: 2:244/322 of query aligns to 19:250/400 of 3ivtB
Q9Y823 Homocitrate synthase, mitochondrial; HCS; EC 2.3.3.14 from Schizosaccharomyces pombe (strain 972 / ATCC 24843) (Fission yeast) (see 2 papers)
24% identity, 75% coverage: 2:244/322 of query aligns to 24:255/418 of Q9Y823
- R43 (= R21) binding ; mutation R->A,K,Q: Abolishes the catalytic activity.
- E44 (≠ D22) binding ; binding ; binding
- Q47 (= Q25) mutation to A: Abolishes the catalytic activity.
- E74 (= E52) mutation to A: Abolishes the catalytic activity.; mutation to Q: Results in a moderate decrease in the turnover number and a slight increase in the Km value for each substrate.
- H103 (≠ A85) binding ; mutation to A: Substantially impairs catalytic efficiency.
- D123 (≠ N105) binding ; mutation to N: Does not affect the catalytic activity but impairs L-lysine inhibition.
- R163 (≠ N145) binding ; mutation R->A,Q: Abolishes the catalytic activity.; mutation to K: Severely diminishes affinity for 2-oxoglutarate and substantially impairs catalytic efficiency.
- S165 (= S147) binding ; mutation to A: Results in a moderate decrease in catalytic efficiency.
- E167 (≠ S149) mutation E->A,Q: Abolishes the catalytic activity.
- T197 (= T185) binding ; binding ; mutation to A: Exhibits a 25-fold decrease in catalytic efficiency.; mutation to S: Results in a modest decrease in catalytic efficiency.; mutation to V: Abolishes the catalytic activity.
- E222 (≠ T211) mutation to Q: Does not affect the catalytic activity but impairs L-lysine inhibition.
- H224 (= H213) binding ; binding
- H226 (= H215) binding ; binding
Sites not aligning to the query:
- 288 R→K: Does not affect the catalytic activity but impairs L-lysine inhibition.
- 332 Y→A: Abolishes the catalytic activity.; Y→F: Results in a decrease in catalytic efficiency.
- 364 Q→R: Does not affect the catalytic activity but impairs L-lysine inhibition.
P11498 Pyruvate carboxylase, mitochondrial; Pyruvic carboxylase; PCB; EC 6.4.1.1 from Homo sapiens (Human) (see 6 papers)
31% identity, 47% coverage: 130:281/322 of query aligns to 687:833/1178 of P11498
- K741 (≠ C183) binding via carbamate group; modified: N6-carboxylysine
- M743 (≠ T185) to I: in PC deficiency; mild; dbSNP:rs28940590
- H771 (= H213) binding
- H773 (= H215) binding
Sites not aligning to the query:
- 145 V → A: in PC deficiency; mild; strongly reduced pyruvate carboxylase activity; dbSNP:rs28940591
- 156 R → Q: in PC deficiency; dbSNP:rs119103241
- 270 R → W: in PC deficiency; dbSNP:rs1258494752
- 304 Y → C: in PC deficiency
- 451 R → C: in PC deficiency; mild; strongly reduced pyruvate carboxylase activity; dbSNP:rs113994143
- 572 binding
- 583 R → L: in PC deficiency; dbSNP:rs119103242
- 610 A → T: in PC deficiency; mild; dbSNP:rs28940589
- 631 R → Q: in PC deficiency; dbSNP:rs113994145
- 1077 mutation F->A,E: Loss of tetramerization and enzyme activity, resulting in an inactive homodimer.
- 1131:1133 natural variant: Missing (in PC deficiency)
- 1144 modified: N6-biotinyllysine
Query Sequence
>RR42_RS13255 FitnessBrowser__Cup4G11:RR42_RS13255
MNASSMLRGPARIEINEVAPRDGLQIEPAVVPTDAKVAFLDALSACGFARIEATSFTSAK
AIPALADAEAVMLRMQRGAGVRYTALVPNLRGLERALSCRPDELNLVMSASETHNRANLR
MTRAQSQAQLLAMVEAANAAGVPVNVSLSTVFGCPFEGEVDADAVMALAESFAHAGAAGI
TLCDTTGMAYPTQVAALCERFQRSLPQAGLTIHLHNTRGMGLANALAAWQTGVTRFDAAA
GGLGGCPFAPGASGNVSTEELVHMFDAMGVDTGVDLARLLDVVAGLPALVQRDTDSQLLR
AGTRLRTHQAPAWLAEHFVGQG
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