SitesBLAST
Comparing GFF2606 PGA1_c26470 2-isopropylmalate synthase LeuA 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)
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)
51% identity, 94% coverage: 8:501/523 of query aligns to 5:502/517 of Q9JZG1
- D16 (= D19) binding
- H204 (= H206) binding
- H206 (= H208) binding
- N240 (= N242) binding
Sites not aligning to the query:
- 366:517 Required for the condensation reaction. Not required to bind substrate
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)
48% identity, 72% coverage: 7:383/523 of query aligns to 82:474/503 of Q9FN52
- G263 (= G177) mutation to E: In gsm2-1; loss of activity and lack of C6, C7 and C8 aliphatic glucosinolates.
6e1jA Crystal structure of methylthioalkylmalate synthase (bjumam1.1) from brassica juncea (see paper)
47% identity, 72% coverage: 6:383/523 of query aligns to 14:407/409 of 6e1jA
- binding coenzyme a: Q30 (= Q22), F60 (= F52), S63 (≠ A55), I95 (≠ L78), R97 (= R80), F121 (= F104), K132 (≠ I114), L133 (≠ P115), S322 (= S301), G323 (= G302), I324 (= I303), D327 (= D306), K331 (= K310), L359 (≠ H335), R362 (= R338), H363 (≠ A339)
- binding 4-(methylsulfanyl)-2-oxobutanoic acid: P192 (= P173), T194 (= T175), H225 (= H206), H227 (= H208)
- binding manganese (ii) ion: D27 (= D19), V82 (≠ R74), E84 (vs. gap), H225 (= H206), H227 (= H208)
Q9FG67 Methylthioalkylmalate synthase 1, chloroplastic; 2-isopropylmalate synthase 3; EC 2.3.3.17 from Arabidopsis thaliana (Mouse-ear cress) (see paper)
46% identity, 75% coverage: 6:395/523 of query aligns to 81:485/506 of Q9FG67
- S102 (≠ T27) mutation to F: In gsm1-1; loss of conversion of C3 to C4 glucosinolates.
- A290 (= A204) mutation to T: In gsm1-2; loss of conversion of C3 to C4 glucosinolates.
3rmjB Crystal structure of truncated alpha-isopropylmalate synthase from neisseria meningitidis (see paper)
53% identity, 61% coverage: 8:326/523 of query aligns to 2:308/308 of 3rmjB
6ktqA Crystal structure of catalytic domain of homocitrate synthase from sulfolobus acidocaldarius (sahcs(dram)) in complex with alpha- ketoglutarate/zn2+/coa (see paper)
37% identity, 68% coverage: 9:365/523 of query aligns to 21:370/399 of 6ktqA
- binding 2-oxoglutaric acid: R30 (= R18), R154 (≠ Q141), T156 (≠ S143), E158 (≠ M145), S184 (≠ N171), T188 (= T175), H216 (= H206), H218 (= H208)
- binding coenzyme a: V67 (≠ A55), R96 (= R80), A97 (= A81), F116 (= F104), H128 (≠ P115), E158 (≠ M145)
- binding zinc ion: E31 (≠ D19), H216 (= H206), H218 (= H208)
4ov9A Structure of isopropylmalate synthase binding with alpha- isopropylmalate (see paper)
34% identity, 71% coverage: 10:382/523 of query aligns to 4:379/380 of 4ov9A
4ov4A Isopropylmalate synthase binding with ketoisovalerate (see paper)
34% identity, 71% coverage: 10:382/523 of query aligns to 4:377/379 of 4ov4A
Q8F3Q1 (R)-citramalate synthase CimA; LiCMS; EC 2.3.3.21 from Leptospira interrogans serogroup Icterohaemorrhagiae serovar Lai (strain 56601) (see 2 papers)
32% identity, 83% coverage: 9:441/523 of query aligns to 7:440/516 of Q8F3Q1
- R16 (= R18) mutation R->K,Q: Loss of activity.
- RD 16:17 (= RD 18:19) binding
- D17 (= D19) 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 (≠ A81) 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 (= F83) mutation to A: 5-fold increase in Km for acetyl-CoA and 120-fold decrease in kcat.
- L104 (≠ I105) mutation to V: 1.8-fold increase in Km for pyruvate and 3.4-fold decrease in kcat.
- Y144 (≠ Q141) 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 (vs. gap) mutation E->D,Q: Minor effects on the binding of acetyl-CoA, but causes a strong decrease in kcat.
- T179 (= T175) binding ; mutation to A: 16.4-fold increase in Km for pyruvate and 186-fold decrease in kcat.
- H302 (= H304) mutation H->A,N: Loss of activity.
- D304 (= D306) mutation to A: 5.2-fold increase in Km for acetyl-CoA and 16.6-fold decrease in kcat.
- N310 (≠ K312) mutation to A: 2.2-fold increase in Km for acetyl-CoA and 1.7-fold decrease in kcat.
- L311 (≠ E313) mutation to A: 8-fold increase in Km for acetyl-CoA and 6-fold decrease in kcat.
- Y312 (≠ T314) mutation to A: Loss of activity.
- Y430 (≠ V431) mutation to L: No change in Km for acetyl-CoA and 2.3-fold decrease in kcat. Severely impairs inhibition by isoleucine.
- D431 (= D432) mutation to A: 1.8-fold decrease in Km for acetyl-CoA and 5-fold decrease in kcat.
Sites not aligning to the query:
- 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.
3ivtB Homocitrate synthase lys4 bound to 2-og (see paper)
31% identity, 70% coverage: 12:377/523 of query aligns to 32:389/400 of 3ivtB
Q9Y823 Homocitrate synthase, mitochondrial; HCS; EC 2.3.3.14 from Schizosaccharomyces pombe (strain 972 / ATCC 24843) (Fission yeast) (see 2 papers)
31% identity, 70% coverage: 12:377/523 of query aligns to 37:394/418 of Q9Y823
- R43 (= R18) binding ; mutation R->A,K,Q: Abolishes the catalytic activity.
- E44 (≠ D19) binding ; binding ; binding
- Q47 (= Q22) mutation to A: Abolishes the catalytic activity.
- E74 (= E49) 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 (≠ L78) binding ; mutation to A: Substantially impairs catalytic efficiency.
- D123 (≠ H102) binding ; mutation to N: Does not affect the catalytic activity but impairs L-lysine inhibition.
- R163 (≠ Q141) binding ; mutation R->A,Q: Abolishes the catalytic activity.; mutation to K: Severely diminishes affinity for 2-oxoglutarate and substantially impairs catalytic efficiency.
- S165 (= S143) binding ; mutation to A: Results in a moderate decrease in catalytic efficiency.
- E167 (≠ M145) mutation E->A,Q: Abolishes the catalytic activity.
- T197 (= T175) 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 (≠ A204) mutation to Q: Does not affect the catalytic activity but impairs L-lysine inhibition.
- H224 (= H206) binding ; binding
- H226 (= H208) binding ; binding
- R288 (≠ M271) mutation to K: Does not affect the catalytic activity but impairs L-lysine inhibition.
- Y332 (≠ F315) mutation to A: Abolishes the catalytic activity.; mutation to F: Results in a decrease in catalytic efficiency.
- Q364 (= Q347) mutation to R: Does not affect the catalytic activity but impairs L-lysine inhibition.
3mi3A Homocitrate synthase lys4 bound to lysine (see paper)
31% identity, 70% coverage: 12:377/523 of query aligns to 14:360/370 of 3mi3A
3ivsA Homocitrate synthase lys4 (see paper)
30% identity, 71% coverage: 12:384/523 of query aligns to 14:360/364 of 3ivsA
O87198 Homocitrate synthase; HCS; EC 2.3.3.14 from Thermus thermophilus (strain ATCC BAA-163 / DSM 7039 / HB27) (see paper)
28% identity, 69% coverage: 12:370/523 of query aligns to 6:358/376 of O87198
- R12 (= R18) binding
- E13 (≠ D19) binding
- H72 (≠ L78) 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 (≠ H102) binding
- R133 (vs. gap) binding
- S135 (= S143) binding
- T166 (= T175) binding ; binding
- H195 (= H206) binding
- H197 (= H208) binding
3bliA Crystal structure of the catalytic domain of licms in complexed with pyruvate and acetyl-coa (see paper)
31% identity, 57% coverage: 9:304/523 of query aligns to 1:296/311 of 3bliA
3hpsA Crystal structure of mycobacterium tuberculosis leua complexed with ketoisocaproate (kic)
28% identity, 93% coverage: 17:500/523 of query aligns to 62:573/575 of 3hpsA
- binding 2-oxo-4-methylpentanoic acid: R63 (= R18), H150 (= H102), Y152 (≠ F104), P235 (= P173), T237 (= T175), H268 (= H206), H270 (= H208)
- binding leucine: G500 (= G429), P501 (= P430), L502 (≠ V431), A503 (≠ D432), D530 (≠ T460), A532 (= A462), Q533 (= Q463), P557 (≠ T484), I559 (≠ T486)
- binding zinc ion: D64 (= D19), H268 (= H206), H270 (= H208)
3hpzB Crystal structure of mycobacterium tuberculosis leua complexed with bromopyruvate
27% identity, 93% coverage: 17:500/523 of query aligns to 62:574/576 of 3hpzB
3figB Crystal structure of leucine-bound leua from mycobacterium tuberculosis (see paper)
27% identity, 93% coverage: 17:500/523 of query aligns to 62:574/577 of 3figB
3a9iA Crystal structure of homocitrate synthase from thermus thermophilus complexed with lys (see paper)
29% identity, 60% coverage: 12:327/523 of query aligns to 5:308/347 of 3a9iA
3hq1A Crystal structure of mycobacterium tuberculosis leua complexed with citrate and mn2+
27% identity, 93% coverage: 17:500/523 of query aligns to 62:571/573 of 3hq1A
Query Sequence
>GFF2606 PGA1_c26470 2-isopropylmalate synthase LeuA
MTTAADKDRVLIFDTTLRDGEQSPGATMTHDEKLEIAELLDDMGVDIIEAGFPIASEGDF
KAVSEIAERSKNSRICGLARANFKDIDRCAEAVKRAAQPRIHTFIGTSPLHRAIPNLTKD
EMAEKIHDTVTHARNLVDNVQWSPMDATRTEWDYLCRVIEIAIKAGATTINIPDTVGYTA
PVESADLIKRLIETVPGADDVIFATHCHNDLGMATANSLAAVAGGARQIECTINGLGERA
GNTALEEVVMALKVRNDIMPFTTGIDTQKIMHISRRVSTVSGFVVQPNKAIVGKNAFAHE
SGIHQDGMLKNKETFEIMRPEDVGIAGTSLPLGKHSGRAALRDKLSQLGFEVGDNQLKDL
FVRFKELADRKKEVFDDDIIALMRTSGDEDDHLKLVSMKVVCGTGGPAEATLEMEVEGKD
VSETAEGDGPVDAAFRAIRKIHPNSAHLQLYQVHAVTEGTDAQATVSVRLEENGVIATGE
SANTDTVVASAAAYIGALNRLIIRRDKMGEGADTREISYKDIT
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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