SitesBLAST
Comparing GFF2101 FitnessBrowser__Marino:GFF2101 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)
P9WQB3 2-isopropylmalate synthase; Alpha-IPM synthase; Alpha-isopropylmalate synthase; EC 2.3.3.13 from Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv) (see 2 papers)
53% identity, 89% coverage: 12:514/564 of query aligns to 54:571/644 of P9WQB3
- R80 (= R38) binding
- T254 (= T212) binding
- H285 (= H243) binding
- H287 (= H245) binding
- 369:424 (vs. 327:372, 55% identical) Subdomain I
- 425:433 (vs. 373:381, 78% identical) Linker
- 434:490 (vs. 382:434, 47% identical) Subdomain II
- N532 (≠ L474) binding
- A536 (≠ E478) binding
- D563 (≠ T506) binding
- A565 (= A508) binding
Sites not aligning to the query:
- 51:368 N-terminal domain
- 426:644 Required for the condensation reaction. Not required to bind substrate
- 491:644 Regulatory domain
- 625 binding
- 627 binding
3figB Crystal structure of leucine-bound leua from mycobacterium tuberculosis (see paper)
50% identity, 95% coverage: 12:547/564 of query aligns to 37:575/577 of 3figB
3hpzB Crystal structure of mycobacterium tuberculosis leua complexed with bromopyruvate
50% identity, 95% coverage: 12:547/564 of query aligns to 37:575/576 of 3hpzB
3hpsA Crystal structure of mycobacterium tuberculosis leua complexed with ketoisocaproate (kic)
50% identity, 95% coverage: 12:547/564 of query aligns to 37:574/575 of 3hpsA
- binding 2-oxo-4-methylpentanoic acid: R63 (= R38), H150 (= H125), Y152 (= Y127), P235 (= P210), T237 (= T212), H268 (= H243), H270 (= H245)
- binding leucine: G500 (= G475), P501 (≠ A476), L502 (≠ V477), A503 (≠ E478), D530 (≠ T506), A532 (= A508), Q533 (≠ N509), P557 (≠ E530), I559 (≠ T532)
- binding zinc ion: D64 (= D39), H268 (= H243), H270 (= H245)
3hq1A Crystal structure of mycobacterium tuberculosis leua complexed with citrate and mn2+
50% identity, 95% coverage: 12:547/564 of query aligns to 37:572/573 of 3hq1A
1sr9A Crystal structure of leua from mycobacterium tuberculosis (see paper)
50% identity, 95% coverage: 12:547/564 of query aligns to 37:572/573 of 1sr9A
4ov9A Structure of isopropylmalate synthase binding with alpha- isopropylmalate (see paper)
30% identity, 63% coverage: 35:391/564 of query aligns to 9:342/380 of 4ov9A
4ov4A Isopropylmalate synthase binding with ketoisovalerate (see paper)
30% identity, 63% coverage: 35:391/564 of query aligns to 9:340/379 of 4ov4A
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)
26% identity, 63% coverage: 11:367/564 of query aligns to 64:412/503 of Q9FN52
- G263 (≠ E214) mutation to E: In gsm2-1; loss of activity and lack of C6, C7 and C8 aliphatic glucosinolates.
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)
25% identity, 94% coverage: 37:564/564 of query aligns to 14:514/517 of Q9JZG1
- D16 (= D39) binding
- H204 (= H243) binding
- H206 (= H245) binding
- N240 (= N279) binding
Sites not aligning to the query:
- 366:517 Required for the condensation reaction. Not required to bind substrate
Q9FG67 Methylthioalkylmalate synthase 1, chloroplastic; 2-isopropylmalate synthase 3; EC 2.3.3.17 from Arabidopsis thaliana (Mouse-ear cress) (see paper)
25% identity, 59% coverage: 11:343/564 of query aligns to 64:398/506 of Q9FG67
- S102 (≠ P47) mutation to F: In gsm1-1; loss of conversion of C3 to C4 glucosinolates.
- A290 (≠ S241) 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)
24% identity, 62% coverage: 20:367/564 of query aligns to 3:345/409 of 6e1jA
- binding coenzyme a: Q30 (= Q42), F60 (= F72), S63 (≠ A75), I95 (≠ L101), R97 (≠ Q103), F121 (≠ Y127), K132 (≠ V138), L133 (≠ F139), S322 (= S334), G323 (= G335), I324 (≠ S336), D327 (= D339), K331 (= K349)
- binding 4-(methylsulfanyl)-2-oxobutanoic acid: P192 (= P210), T194 (= T212), H225 (= H243), H227 (= H245)
- binding manganese (ii) ion: D27 (= D39), V82 (≠ I92), E84 (= E94), H225 (= H243), H227 (= H245)
Sites not aligning to the query:
3rmjB Crystal structure of truncated alpha-isopropylmalate synthase from neisseria meningitidis (see paper)
28% identity, 52% coverage: 37:331/564 of query aligns to 11:293/308 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)
25% identity, 63% coverage: 37:391/564 of query aligns to 29:352/399 of 6ktqA
- binding 2-oxoglutaric acid: R30 (= R38), R154 (≠ Q172), T156 (≠ S174), E158 (= E176), S184 (≠ N208), T188 (= T212), H216 (= H243), H218 (= H245)
- binding coenzyme a: V67 (≠ A75), R96 (= R105), A97 (≠ P106), F116 (≠ Y127), H128 (≠ F139), E158 (= E176)
- binding zinc ion: E31 (≠ D39), H216 (= H243), H218 (= H245)
2ztjA Crystal structure of homocitrate synthase from thermus thermophilus complexed with alpha-ketoglutarate (see paper)
26% identity, 55% coverage: 32:341/564 of query aligns to 4:288/312 of 2ztjA
3ivtB Homocitrate synthase lys4 bound to 2-og (see paper)
24% identity, 54% coverage: 37:341/564 of query aligns to 37:320/400 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, 54% coverage: 37:341/564 of query aligns to 42:325/418 of Q9Y823
- R43 (= R38) binding ; mutation R->A,K,Q: Abolishes the catalytic activity.
- E44 (≠ D39) binding ; binding ; binding
- Q47 (= Q42) mutation to A: Abolishes the catalytic activity.
- E74 (= E69) 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 (≠ Q103) binding ; mutation to A: Substantially impairs catalytic efficiency.
- D123 (≠ H125) binding ; mutation to N: Does not affect the catalytic activity but impairs L-lysine inhibition.
- R163 (≠ Q168) binding ; mutation R->A,Q: Abolishes the catalytic activity.; mutation to K: Severely diminishes affinity for 2-oxoglutarate and substantially impairs catalytic efficiency.
- S165 (≠ T170) binding ; mutation to A: Results in a moderate decrease in catalytic efficiency.
- E167 (= E182) mutation E->A,Q: Abolishes the catalytic activity.
- T197 (= T212) 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 (≠ S241) mutation to Q: Does not affect the catalytic activity but impairs L-lysine inhibition.
- H224 (= H243) binding ; binding
- H226 (= H245) binding ; binding
- R288 (≠ A304) mutation to K: Does not affect the catalytic activity but impairs L-lysine inhibition.
Sites not aligning to the query:
- 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.
Q8F3Q1 (R)-citramalate synthase CimA; LiCMS; EC 2.3.3.21 from Leptospira interrogans serogroup Icterohaemorrhagiae serovar Lai (strain 56601) (see 2 papers)
22% identity, 89% coverage: 35:537/564 of query aligns to 13:489/516 of Q8F3Q1
- R16 (= R38) mutation R->K,Q: Loss of activity.
- RD 16:17 (= RD 38:39) binding
- D17 (= D39) 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 (≠ V124) 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 (≠ V126) mutation to A: 5-fold increase in Km for acetyl-CoA and 120-fold decrease in kcat.
- L104 (≠ V157) mutation to V: 1.8-fold increase in Km for pyruvate and 3.4-fold decrease in kcat.
- Y144 (≠ V193) 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 (= E195) mutation E->D,Q: Minor effects on the binding of acetyl-CoA, but causes a strong decrease in kcat.
- T179 (= T212) binding ; mutation to A: 16.4-fold increase in Km for pyruvate and 186-fold decrease in kcat.
- H302 (= H337) mutation H->A,N: Loss of activity.
- D304 (= D339) mutation to A: 5.2-fold increase in Km for acetyl-CoA and 16.6-fold decrease in kcat.
- N310 (= N355) mutation to A: 2.2-fold increase in Km for acetyl-CoA and 1.7-fold decrease in kcat.
- L311 (≠ V356) mutation to A: 8-fold increase in Km for acetyl-CoA and 6-fold decrease in kcat.
- Y312 (≠ A357) mutation to A: Loss of activity.
- Y430 (≠ V477) mutation to L: No change in Km for acetyl-CoA and 2.3-fold decrease in kcat. Severely impairs inhibition by isoleucine.
- D431 (≠ E478) mutation to A: 1.8-fold decrease in Km for acetyl-CoA and 5-fold decrease in kcat.
- L451 (≠ E495) mutation to V: 1.5-fold increase in Km for acetyl-CoA and 4.3 decrease in kcat.
- Y454 (≠ D498) 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 (≠ L502) mutation to A: 1.3-fold decrease in Km for acetyl-CoA and 14-fold decrease in kcat. Abolishes inhibition by isoleucine.
- T464 (≠ A508) mutation to A: 1.8-fold decrease in Km for acetyl-CoA and 4.3-fold decrease in kcat.
- V468 (≠ A512) 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.
Sites not aligning to the query:
- 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.
O87198 Homocitrate synthase; HCS; EC 2.3.3.14 from Thermus thermophilus (strain ATCC BAA-163 / DSM 7039 / HB27) (see paper)
25% identity, 55% coverage: 32:341/564 of query aligns to 4:296/376 of O87198
- R12 (= R38) binding
- E13 (≠ D39) binding
- H72 (≠ Q103) 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 (≠ V124) binding
- R133 (≠ Q168) binding
- S135 (≠ T170) binding
- T166 (= T212) binding ; binding
- H195 (= H243) binding
- H197 (= H245) binding
3a9iA Crystal structure of homocitrate synthase from thermus thermophilus complexed with lys (see paper)
25% identity, 55% coverage: 32:341/564 of query aligns to 3:289/347 of 3a9iA
Query Sequence
>GFF2101 FitnessBrowser__Marino:GFF2101
MAFDHRKYVAFKPVAKTDRRWPDKVIEKAPTWCAVDLRDGNQALVKPMSVAQKTRMFELL
VKLGFKEIEIGFPAASQPDFDFCRKLIEENRIPEDVKIQVLTQARPELIERTYEALAGAR
KAIVHVYNSTSTVQREQVFGLDRDGIRDIAVNGAKLVRDIAARHPETQWTFQYSPESFTG
TELDFAAEVIDAVSEVWRPEEGQPMIINLPATVEMATPNVFADQIEWICDNIQRREHISI
SVHTHNDRGCAVAAAELAVMAGADRVEGTLMGNGERTGNMDLVTMAMNLYSQGIDPTLDL
SGMAEITEVVEACTEISTHPRHPYAGELVFTAFSGSHQDAIRKCLARRKDGETWNVAYLP
IDPFDVGRRYEEVVRINSQSGKGGVAYVLERDYNISLPRWLQIEFSKVVQREAETNGGEI
DSLTIHRLFEDRYLKVHADWALRSYDLHRDEEGVHAEVSVGRDASPVRLDGHGLGAVEAV
SEALEKRFGISIAVEAYDEFALGEGTNANALACIRLTASGMHCSAAALAEDTTSATLQAL
FSAVAQAVGIEMPEKEAEPEAAGA
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