SitesBLAST
Comparing 7026628 Shewana3_3761 2-isopropylmalate synthase (RefSeq) 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)
47% identity, 95% coverage: 2:498/522 of query aligns to 4:500/517 of Q9JZG1
- D16 (= D14) binding
- H204 (= H202) binding
- H206 (= H204) binding
- N240 (= N238) binding
Sites not aligning to the query:
- 366:517 Required for the condensation reaction. Not required to bind substrate
3rmjB Crystal structure of truncated alpha-isopropylmalate synthase from neisseria meningitidis (see paper)
55% identity, 61% coverage: 2:321/522 of query aligns to 1:307/308 of 3rmjB
Q9FG67 Methylthioalkylmalate synthase 1, chloroplastic; 2-isopropylmalate synthase 3; EC 2.3.3.17 from Arabidopsis thaliana (Mouse-ear cress) (see paper)
45% identity, 72% coverage: 3:378/522 of query aligns to 83:473/506 of Q9FG67
- S102 (= S22) mutation to F: In gsm1-1; loss of conversion of C3 to C4 glucosinolates.
- A290 (≠ S200) 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)
44% identity, 72% coverage: 3:378/522 of query aligns to 16:406/409 of 6e1jA
- binding coenzyme a: Q30 (= Q17), F60 (= F47), S63 (= S50), I95 (≠ L73), R97 (= R75), F121 (= F99), K132 (= K110), L133 (= L111), S322 (= S297), G323 (= G298), I324 (= I299), D327 (= D302), K331 (= K306), L359 (≠ R331), R362 (= R334), H363 (= H335)
- binding 4-(methylsulfanyl)-2-oxobutanoic acid: P192 (= P169), T194 (= T171), H225 (= H202), H227 (= H204)
- binding manganese (ii) ion: D27 (= D14), V82 (vs. gap), E84 (vs. gap), H225 (= H202), H227 (= H204)
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)
42% identity, 74% coverage: 3:390/522 of query aligns to 83:485/503 of Q9FN52
- G263 (= G173) mutation to E: In gsm2-1; loss of activity and lack of C6, C7 and C8 aliphatic glucosinolates.
6ktqA Crystal structure of catalytic domain of homocitrate synthase from sulfolobus acidocaldarius (sahcs(dram)) in complex with alpha- ketoglutarate/zn2+/coa (see paper)
32% identity, 67% coverage: 4:354/522 of query aligns to 21:363/399 of 6ktqA
- binding 2-oxoglutaric acid: R30 (= R13), R154 (≠ E137), T156 (≠ S139), E158 (= E141), S184 (≠ N167), T188 (= T171), H216 (= H202), H218 (= H204)
- binding coenzyme a: V67 (≠ S50), R96 (= R75), A97 (= A76), F116 (= F99), H128 (≠ L111), E158 (= E141)
- binding zinc ion: E31 (≠ D14), H216 (= H202), H218 (= H204)
4ov9A Structure of isopropylmalate synthase binding with alpha- isopropylmalate (see paper)
35% identity, 65% coverage: 7:345/522 of query aligns to 6:344/380 of 4ov9A
4ov4A Isopropylmalate synthase binding with ketoisovalerate (see paper)
35% identity, 65% coverage: 7:345/522 of query aligns to 6:342/379 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)
27% identity, 95% coverage: 1:498/522 of query aligns to 4:508/516 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 (= L73) 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 (vs. gap) mutation to A: 5-fold increase in Km for acetyl-CoA and 120-fold decrease in kcat.
- L104 (≠ A91) mutation to V: 1.8-fold increase in Km for pyruvate and 3.4-fold decrease in kcat.
- Y144 (≠ S139) 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 (= E141) mutation E->D,Q: Minor effects on the binding of acetyl-CoA, but causes a strong decrease in kcat.
- T179 (= T171) binding ; mutation to A: 16.4-fold increase in Km for pyruvate and 186-fold decrease in kcat.
- H302 (= H300) mutation H->A,N: Loss of activity.
- D304 (= D302) mutation to A: 5.2-fold increase in Km for acetyl-CoA and 16.6-fold decrease in kcat.
- N310 (≠ Q308) mutation to A: 2.2-fold increase in Km for acetyl-CoA and 1.7-fold decrease in kcat.
- L311 (≠ N309) mutation to A: 8-fold increase in Km for acetyl-CoA and 6-fold decrease in kcat.
- Y312 (≠ T310) mutation to A: Loss of activity.
- Y430 (≠ V430) mutation to L: No change in Km for acetyl-CoA and 2.3-fold decrease in kcat. Severely impairs inhibition by isoleucine.
- D431 (= D431) mutation to A: 1.8-fold decrease in Km for acetyl-CoA and 5-fold decrease in kcat.
- L451 (≠ I447) mutation to V: 1.5-fold increase in Km for acetyl-CoA and 4.3 decrease in kcat.
- Y454 (= Y450) 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 (≠ A454) mutation to A: 1.3-fold decrease in Km for acetyl-CoA and 14-fold decrease in kcat. Abolishes inhibition by isoleucine.
- T464 (vs. gap) mutation to A: 1.8-fold decrease in Km for acetyl-CoA and 4.3-fold decrease in kcat.
- V468 (≠ G463) mutation to A: No change in Km for acetyl-CoA and 2-fold decrease in kcat. Increases inhibition by isoleucine and leucine becomes an effective inhibitor.
- P493 (≠ T483) mutation to A: 1.5-fold decrease in Km for acetyl-CoA and 2.6-fold decrease in kcat.
- Q495 (≠ V485) mutation to A: 1.6-fold decrease in Km for acetyl-CoA and 2.8-fold decrease in kcat.
Q9Y823 Homocitrate synthase, mitochondrial; HCS; EC 2.3.3.14 from Schizosaccharomyces pombe (strain 972 / ATCC 24843) (Fission yeast) (see 2 papers)
30% identity, 71% coverage: 3:372/522 of query aligns to 33:393/418 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 (≠ A76) binding ; mutation to A: Substantially impairs catalytic efficiency.
- D123 (≠ H97) binding ; mutation to N: Does not affect the catalytic activity but impairs L-lysine inhibition.
- R163 (≠ E137) binding ; mutation R->A,Q: Abolishes the catalytic activity.; mutation to K: Severely diminishes affinity for 2-oxoglutarate and substantially impairs catalytic efficiency.
- S165 (= S139) binding ; mutation to A: Results in a moderate decrease in catalytic efficiency.
- E167 (= E141) mutation E->A,Q: Abolishes the catalytic activity.
- T197 (= T171) 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 (≠ S200) mutation to Q: Does not affect the catalytic activity but impairs L-lysine inhibition.
- H224 (= H202) binding ; binding
- H226 (= H204) binding ; binding
- R288 (≠ H267) mutation to K: Does not affect the catalytic activity but impairs L-lysine inhibition.
- Y332 (= Y311) mutation to A: Abolishes the catalytic activity.; mutation to F: Results in a decrease in catalytic efficiency.
- Q364 (≠ E343) mutation to R: Does not affect the catalytic activity but impairs L-lysine inhibition.
3ivtB Homocitrate synthase lys4 bound to 2-og (see paper)
30% identity, 71% coverage: 3:372/522 of query aligns to 28:388/400 of 3ivtB
3mi3A Homocitrate synthase lys4 bound to lysine (see paper)
29% identity, 71% coverage: 3:372/522 of query aligns to 10:359/370 of 3mi3A
O87198 Homocitrate synthase; HCS; EC 2.3.3.14 from Thermus thermophilus (strain ATCC BAA-163 / DSM 7039 / HB27) (see paper)
29% identity, 70% coverage: 7:370/522 of query aligns to 6:361/376 of O87198
- R12 (= R13) binding
- E13 (≠ D14) binding
- H72 (≠ A76) 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 (≠ H97) binding
- R133 (vs. gap) binding
- S135 (= S139) binding
- T166 (= T171) binding ; binding
- H195 (= H202) binding
- H197 (= H204) binding
3ivsA Homocitrate synthase lys4 (see paper)
29% identity, 66% coverage: 3:349/522 of query aligns to 10:334/364 of 3ivsA
3bliA Crystal structure of the catalytic domain of licms in complexed with pyruvate and acetyl-coa (see paper)
30% identity, 57% coverage: 4:300/522 of query aligns to 1:296/311 of 3bliA
2zyfA Crystal structure of homocitrate synthase from thermus thermophilus complexed with magnesuim ion and alpha-ketoglutarate (see paper)
29% identity, 61% coverage: 7:324/522 of query aligns to 6:310/314 of 2zyfA
2ztjA Crystal structure of homocitrate synthase from thermus thermophilus complexed with alpha-ketoglutarate (see paper)
28% identity, 61% coverage: 7:324/522 of query aligns to 6:308/312 of 2ztjA
3a9iA Crystal structure of homocitrate synthase from thermus thermophilus complexed with lys (see paper)
28% identity, 61% coverage: 7:322/522 of query aligns to 5:307/347 of 3a9iA
3figB Crystal structure of leucine-bound leua from mycobacterium tuberculosis (see paper)
26% identity, 94% coverage: 12:502/522 of query aligns to 62:577/577 of 3figB
3hq1A Crystal structure of mycobacterium tuberculosis leua complexed with citrate and mn2+
26% identity, 93% coverage: 12:498/522 of query aligns to 62:570/573 of 3hq1A
Query Sequence
>7026628 Shewana3_3761 2-isopropylmalate synthase (RefSeq)
MSNRVIIFDTTLRDGEQALAASLSVKEKLQIAMALERLGVDVMEVGFPVSSPGDFESVQT
IARTIKNSRVCALSRALEKDIDAAAQALSVAEQFRIHTFISTSTIHVESKLKRSFEQVLE
MAVGAVKYARRFTDDVEFSCEDAGRTPIDNLCRMVEAAIHAGARTINIPDTVGYTVPSEF
GGIIQTLFNRVPNIDQAIISVHCHDDLGMSVANSITAVQHGARQIECTMNGIGERAGNCS
LEEIAMILATRKNLLGVETGINAKEIHRTSNLVSQLCNMPIQSNKAIVGANAFTHSSGIH
QDGMLKAQNTYEIMTPESIGLNRNNLNMTSRSGRHVIKHRMEEMGYSEQDFNLDALYEQF
LHLADKKGQVFDYDLEALAFMEAQAAEDNFYQLQQLVVQSDSTEGVATATVRIDVGGEIK
TEAATGNGPVDAAYNAIARATDRRIDIISYKLGAKGEGQNALGQVDITAVYHEQNFHGVG
LATDVVEASARALVHVMNLTCRADKVADYKQNMHKNRELGGV
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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