SitesBLAST
Comparing 8499505 FitnessBrowser__Miya:8499505 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)
Q9FG67 Methylthioalkylmalate synthase 1, chloroplastic; 2-isopropylmalate synthase 3; EC 2.3.3.17 from Arabidopsis thaliana (Mouse-ear cress) (see paper)
30% identity, 65% coverage: 5:357/540 of query aligns to 85:447/506 of Q9FG67
- S102 (≠ N22) mutation to F: In gsm1-1; loss of conversion of C3 to C4 glucosinolates.
- A290 (≠ G205) mutation to T: In gsm1-2; loss of conversion of C3 to C4 glucosinolates.
6e1jA Crystal structure of methylthioalkylmalate synthase (bjumam1.1) from brassica juncea (see paper)
30% identity, 65% coverage: 5:357/540 of query aligns to 18:380/409 of 6e1jA
- binding coenzyme a: Q30 (= Q17), F60 (≠ W47), S63 (= S50), I95 (≠ T83), R97 (≠ D85), F121 (= F104), K132 (≠ A115), L133 (= L116), S322 (≠ G303), G323 (= G304), I324 (≠ V305), D327 (≠ S308), K331 (≠ R312), L359 (= L336), R362 (= R339), H363 (≠ S340)
- binding 4-(methylsulfanyl)-2-oxobutanoic acid: P192 (≠ C177), T194 (= T179), H225 (= H207), H227 (= H209)
- binding manganese (ii) ion: D27 (= D14), V82 (= V70), E84 (≠ S72), H225 (= H207), H227 (= H209)
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)
27% identity, 84% coverage: 1:451/540 of query aligns to 3:439/517 of Q9JZG1
- D16 (= D14) binding
- H204 (= H207) binding
- H206 (= H209) binding
- N240 (= N243) binding
Sites not aligning to the query:
- 366:517 Required for the condensation reaction. Not required to bind substrate
6ktqA Crystal structure of catalytic domain of homocitrate synthase from sulfolobus acidocaldarius (sahcs(dram)) in complex with alpha- ketoglutarate/zn2+/coa (see paper)
28% identity, 69% coverage: 4:375/540 of query aligns to 21:377/399 of 6ktqA
- binding 2-oxoglutaric acid: R30 (= R13), R154 (≠ Y142), T156 (≠ D144), E158 (= E146), S184 (≠ V175), T188 (= T179), H216 (= H207), H218 (= H209)
- binding coenzyme a: V67 (≠ S50), R96 (≠ P80), A97 (≠ N81), F116 (= F104), H128 (≠ L116), E158 (= E146)
- binding zinc ion: E31 (≠ D14), H216 (= H207), H218 (= H209)
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)
29% identity, 65% coverage: 5:357/540 of query aligns to 85:447/503 of Q9FN52
- G263 (= G181) mutation to E: In gsm2-1; loss of activity and lack of C6, C7 and C8 aliphatic glucosinolates.
O87198 Homocitrate synthase; HCS; EC 2.3.3.14 from Thermus thermophilus (strain ATCC BAA-163 / DSM 7039 / HB27) (see paper)
30% identity, 66% coverage: 3:357/540 of query aligns to 2:344/376 of O87198
- R12 (= R13) binding
- E13 (≠ D14) binding
- H72 (= H79) binding ; mutation to L: Significant decrease in sensitivity to lysine inhibition. Large decrease in affinity for 2-oxoglutarate. Almost no effect on affinity for acetyl-CoA and on turnover number.
- D92 (≠ A101) binding
- R133 (≠ Y142) binding
- S135 (≠ D144) binding
- T166 (= T179) binding ; binding
- H195 (= H207) binding
- H197 (= H209) binding
4ov9A Structure of isopropylmalate synthase binding with alpha- isopropylmalate (see paper)
28% identity, 66% coverage: 3:356/540 of query aligns to 2:350/380 of 4ov9A
4ov4A Isopropylmalate synthase binding with ketoisovalerate (see paper)
28% identity, 66% coverage: 3:356/540 of query aligns to 2:348/379 of 4ov4A
3rmjB Crystal structure of truncated alpha-isopropylmalate synthase from neisseria meningitidis (see paper)
29% identity, 56% coverage: 2:302/540 of query aligns to 1:295/308 of 3rmjB
2zyfA Crystal structure of homocitrate synthase from thermus thermophilus complexed with magnesuim ion and alpha-ketoglutarate (see paper)
30% identity, 61% coverage: 3:333/540 of query aligns to 2:313/314 of 2zyfA
3a9iA Crystal structure of homocitrate synthase from thermus thermophilus complexed with lys (see paper)
30% identity, 60% coverage: 3:326/540 of query aligns to 1:305/347 of 3a9iA
2ztjA Crystal structure of homocitrate synthase from thermus thermophilus complexed with alpha-ketoglutarate (see paper)
29% identity, 61% coverage: 3:333/540 of query aligns to 2:311/312 of 2ztjA
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, 88% coverage: 4:480/540 of query aligns to 7:464/516 of Q8F3Q1
- R16 (= R13) mutation R->K,Q: Loss of activity.
- RD 16:17 (= RD 13:14) binding
- D17 (= D14) 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 (≠ F74) 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 (≠ T83) mutation to A: 5-fold increase in Km for acetyl-CoA and 120-fold decrease in kcat.
- L104 (≠ F104) mutation to V: 1.8-fold increase in Km for pyruvate and 3.4-fold decrease in kcat.
- Y144 (= Y142) 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 (= E146) mutation E->D,Q: Minor effects on the binding of acetyl-CoA, but causes a strong decrease in kcat.
- T179 (= T179) binding ; mutation to A: 16.4-fold increase in Km for pyruvate and 186-fold decrease in kcat.
- H302 (= H306) mutation H->A,N: Loss of activity.
- D304 (≠ S308) mutation to A: 5.2-fold increase in Km for acetyl-CoA and 16.6-fold decrease in kcat.
- N310 (≠ S315) mutation to A: 2.2-fold increase in Km for acetyl-CoA and 1.7-fold decrease in kcat.
- L311 (= L316) mutation to A: 8-fold increase in Km for acetyl-CoA and 6-fold decrease in kcat.
- Y312 (= Y317) mutation to A: Loss of activity.
- Y430 (≠ V444) mutation to L: No change in Km for acetyl-CoA and 2.3-fold decrease in kcat. Severely impairs inhibition by isoleucine.
- D431 (≠ N445) mutation to A: 1.8-fold decrease in Km for acetyl-CoA and 5-fold decrease in kcat.
- L451 (= L467) mutation to V: 1.5-fold increase in Km for acetyl-CoA and 4.3 decrease in kcat.
- Y454 (≠ F470) mutation to A: 1.4 decrease in Km for acetyl-CoA and 17-fold decrease in kcat. Still inhibited by isoleucine and weakly inhibited by leucine.
- I458 (≠ V474) mutation to A: 1.3-fold decrease in Km for acetyl-CoA and 14-fold decrease in kcat. Abolishes inhibition by isoleucine.
- T464 (= T480) mutation to A: 1.8-fold decrease in Km for acetyl-CoA and 4.3-fold decrease in kcat.
Sites not aligning to the query:
- 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.
3ivtB Homocitrate synthase lys4 bound to 2-og (see paper)
27% identity, 68% coverage: 7:373/540 of query aligns to 32:382/400 of 3ivtB
Q9Y823 Homocitrate synthase, mitochondrial; HCS; EC 2.3.3.14 from Schizosaccharomyces pombe (strain 972 / ATCC 24843) (Fission yeast) (see 2 papers)
27% identity, 68% coverage: 7:373/540 of query aligns to 37:387/418 of Q9Y823
- R43 (= R13) binding ; mutation R->A,K,Q: Abolishes the catalytic activity.
- E44 (≠ D14) binding ; binding ; binding
- Q47 (= Q17) mutation to A: Abolishes the catalytic activity.
- E74 (= E44) 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 (= H78) binding ; mutation to A: Substantially impairs catalytic efficiency.
- D123 (≠ S107) binding ; mutation to N: Does not affect the catalytic activity but impairs L-lysine inhibition.
- R163 (≠ Y142) binding ; mutation R->A,Q: Abolishes the catalytic activity.; mutation to K: Severely diminishes affinity for 2-oxoglutarate and substantially impairs catalytic efficiency.
- S165 (≠ D144) binding ; mutation to A: Results in a moderate decrease in catalytic efficiency.
- E167 (= E146) mutation E->A,Q: Abolishes the catalytic activity.
- T197 (= T179) 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 (≠ G205) mutation to Q: Does not affect the catalytic activity but impairs L-lysine inhibition.
- H224 (= H207) binding ; binding
- H226 (= H209) binding ; binding
- R288 (≠ T273) mutation to K: Does not affect the catalytic activity but impairs L-lysine inhibition.
- Y332 (= Y317) mutation to A: Abolishes the catalytic activity.; mutation to F: Results in a decrease in catalytic efficiency.
- Q364 (≠ R348) mutation to R: Does not affect the catalytic activity but impairs L-lysine inhibition.
3mi3A Homocitrate synthase lys4 bound to lysine (see paper)
26% identity, 68% coverage: 7:373/540 of query aligns to 14:353/370 of 3mi3A
3ivsA Homocitrate synthase lys4 (see paper)
27% identity, 66% coverage: 7:361/540 of query aligns to 14:341/364 of 3ivsA
3bliA Crystal structure of the catalytic domain of licms in complexed with pyruvate and acetyl-coa (see paper)
26% identity, 57% coverage: 4:309/540 of query aligns to 1:299/311 of 3bliA
Q53WI0 4-hydroxy-2-oxovalerate aldolase; HOA; 4-hydroxy-2-keto-pentanoic acid aldolase; 4-hydroxy-2-oxohexanoate aldolase; 4-hydroxy-2-oxopentanoate aldolase; EC 4.1.3.39; EC 4.1.3.43 from Thermus thermophilus (strain ATCC 27634 / DSM 579 / HB8) (see paper)
28% identity, 54% coverage: 9:300/540 of query aligns to 15:285/347 of Q53WI0
Sites not aligning to the query:
- 324 A→G: Increases the channeling efficiency of propanaldehyde from 57% to 94%.
P51015 4-hydroxy-2-oxovalerate aldolase 4; HOA 4; 4-hydroxy-2-keto-pentanoic acid aldolase 4; 4-hydroxy-2-oxohexanoate aldolase; 4-hydroxy-2-oxopentanoate aldolase 4; EC 4.1.3.39; EC 4.1.3.43 from Paraburkholderia xenovorans (strain LB400) (see 3 papers)
28% identity, 42% coverage: 3:230/540 of query aligns to 6:222/346 of P51015
- R16 (= R13) mutation to A: Loss of aldol cleavage activity.; mutation to K: 4000-fold decrease in the catalytic efficiency of the aldol cleavage reaction.
- H20 (≠ Q17) mutation H->A,S: 100-fold decrease in the catalytic efficiency of the aldol cleavage reaction. Dramatic reduction in acetaldehyde and propanaldehyde channeling efficiency by more than 70%.
- L87 (≠ F74) mutation to A: 32-fold reduction in the catalytic efficiency with acetaldehyde as substrate of the aldol addition reaction, but no change in the catalytic efficiency using propanaldehyde; thus, exhibits a 40-fold preference for propanaldehyde over acetaldehyde.; mutation L->N,W: Loss of aldolase activity (with either enantiomer of HOPA), but retains some decarboxylase activity for the smaller oxaloacetate substrate. In the retro-aldol cleavage reaction, is inactive toward 4(S)-HOPA but is active toward 4(R)-HOPA, albeit with a great reduction in catalytic efficiency, and in the aldol addition reaction, produces also exclusively the 4(R)-enantiomer; when associated with F-290.
- L89 (vs. gap) mutation to A: As the wild-type enzyme, exhibits similar catalytic efficiency with acetaldehyde or propanaldehyde as substrate in the aldol addition reaction but displays higher catalytic efficiency with longer aldehydes (50-fold increase using pentaldehyde). Shows a reduction in aldehyde channeling efficiency by 30%.
Sites not aligning to the query:
- 290 Y→F: Loss of stereochemical control as the mutant is able to catalyze the aldol cleavage of substrates with both R and S configurations at C4 with similar kinetic parameters. 3.5-fold decrease in the catalytic efficiency of the aldol cleavage reaction. Reduction in aldehyde channeling efficiency by more than 30%. In the retro-aldol cleavage reaction, is inactive toward 4(S)-HOPA but is active toward 4(R)-HOPA, albeit with a great reduction in catalytic efficiency, and in the aldol addition reaction, produces also exclusively the 4(R)-enantiomer; when associated with N-87 or W-87.; Y→S: Loss of stereochemical control as the mutant is able to catalyze the aldol cleavage of substrates with both R and S configurations at C4 with similar kinetic parameters. 3.5-fold decrease in the catalytic efficiency of the aldol cleavage reaction.
- 322 G→A: Displays a reduction in aldehyde channeling efficiency of about 20%.; mutation G->F,L: Unable to channel either acetaldehyde or propanaldehyde.
- 323 G→A: Able to channel butyraldehyde (with less efficiency than wild-type) but not its isomer isobutyraldehyde.; G→F: Unable to channel either acetaldehyde or propanaldehyde.; G→L: Able to channel acetaldehyde but not the larger propanaldehyde.
Query Sequence
>8499505 FitnessBrowser__Miya:8499505
MTRRIQLYDTTLRDGSQSEDINLTAADKLKIALKLDEIGIDRIEGGWPGSNPVDVAFFKE
IANYHLKHAVISAFGSTHHPNFTADSDPNLRAIAESGARVASIFGKSCEVHAAEALRLDA
ARNLEIIGDSVAFLKGKLAEVYFDAEHFFDGYRHNAAYALSALRRAHEAGADVLVLCDTN
GGTLPHEVARIVTEVREALPGAAVGIHAHNDCELAVANSIAAVQAGAVQIQGTINGVGER
CGNANLCSIIPTLELKFGGEYTCLPEGRLQQLTAVAAYVSEVANIPPFSRQPYVGRSAFA
HKGGVHVSAVNRKSSLYEHISPDVVGNRQRILITELAGRSNIVSLARRFGFHLDKDEPVV
KGLLTELKKKASLGYDYAAAEASVELLILRKLARRGVREFFRLLQFRVLETKHDSEGEPV
SEVSVMVDVEGVTEHTAATGRGPVNALDNALRKALLGFYPRLSEMRLLDFKVRVLTGAET
GGGTASTVRVLIESGDSDSRWVTVGVSFNIIEASWQALADSVTYKLYKDEHARRAGSDGE
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