SitesBLAST
Comparing RR42_RS27900 FitnessBrowser__Cup4G11:RR42_RS27900 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)
1nvmA Crystal structure of a bifunctional aldolase-dehydrogenase : sequestering a reactive and volatile intermediate (see paper)
83% identity, 99% coverage: 5:337/338 of query aligns to 6:338/340 of 1nvmA
- active site: D17 (= D16), H20 (= H19), H199 (= H198), H201 (= H200), Y290 (= Y289)
- binding manganese (ii) ion: D17 (= D16), H199 (= H198), H201 (= H200)
- binding oxalate ion: R16 (= R15), F138 (= F137), M140 (= M139), S170 (= S169), H199 (= H198), H201 (= H200), Y290 (= Y289)
P51016 4-hydroxy-2-oxovalerate aldolase; HOA; 4-hydroxy-2-keto-pentanoic acid aldolase; 4-hydroxy-2-oxopentanoate aldolase; EC 4.1.3.39 from Pseudomonas sp. (strain CF600) (see 2 papers)
83% identity, 99% coverage: 5:337/338 of query aligns to 7:339/345 of P51016
- D18 (= D16) binding
- H200 (= H198) binding
- H202 (= H200) binding
Sites not aligning to the query:
- 1 modified: Initiator methionine, Removed
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)
57% identity, 99% coverage: 5:338/338 of query aligns to 6:339/346 of P51015
- R16 (= R15) mutation to A: Loss of aldol cleavage activity.; mutation to K: 4000-fold decrease in the catalytic efficiency of the aldol cleavage reaction.
- H20 (= H19) 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 (= L86) 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 (= L88) 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%.
- Y290 (= Y289) mutation to 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.; mutation to 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.
- G322 (= G321) mutation to A: Displays a reduction in aldehyde channeling efficiency of about 20%.; mutation G->F,L: Unable to channel either acetaldehyde or propanaldehyde.
- G323 (= G322) mutation to A: Able to channel butyraldehyde (with less efficiency than wild-type) but not its isomer isobutyraldehyde.; mutation to F: Unable to channel either acetaldehyde or propanaldehyde.; mutation to L: Able to channel acetaldehyde but not the larger propanaldehyde.
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)
52% identity, 98% coverage: 5:334/338 of query aligns to 9:337/347 of Q53WI0
- A324 (≠ G321) mutation to G: Increases the channeling efficiency of propanaldehyde from 57% to 94%.
4lrsA Crystal and solution structures of the bifunctional enzyme (aldolase/aldehyde dehydrogenase) from thermomonospora curvata, reveal a cofactor-binding domain motion during NAD+ and coa accommodation whithin the shared cofactor-binding site
52% identity, 99% coverage: 5:338/338 of query aligns to 2:335/337 of 4lrsA
- active site: D13 (= D16), H16 (= H19), H195 (= H198), H197 (= H200), Y286 (= Y289)
- binding magnesium ion: D13 (= D16), H195 (= H198), H197 (= H200)
- binding pyruvic acid: R12 (= R15), D13 (= D16), F134 (= F137), M136 (= M139), V164 (= V167), S166 (= S169), H195 (= H198), H197 (= H200), Y286 (= Y289)
4jn6C Crystal structure of the aldolase-dehydrogenase complex from mycobacterium tuberculosis hrv37 (see paper)
50% identity, 97% coverage: 7:334/338 of query aligns to 4:331/339 of 4jn6C
- active site: D13 (= D16), H16 (= H19), H195 (= H198), H197 (= H200), Y286 (= Y289)
- binding manganese (ii) ion: D13 (= D16), H195 (= H198), H197 (= H200)
- binding oxalate ion: R12 (= R15), M136 (= M139), V164 (= V167), S166 (= S169), H195 (= H198), H197 (= H200), Y286 (= Y289)
P9WMK5 4-hydroxy-2-oxohexanoate aldolase; 4-hydroxy-2-keto-pentanoic acid aldolase; 4-hydroxy-2-oxopentanoate aldolase; 4-hydroxy-2-oxovalerate aldolase; HOA; EC 4.1.3.43; EC 4.1.3.39 from Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv) (see paper)
50% identity, 97% coverage: 7:334/338 of query aligns to 7:334/346 of P9WMK5
- D16 (= D16) binding
- H198 (= H198) binding
- H200 (= H200) binding
- G322 (= G322) mutation to F: Abolishes substrate channeling to HsaG.
6ktqA Crystal structure of catalytic domain of homocitrate synthase from sulfolobus acidocaldarius (sahcs(dram)) in complex with alpha- ketoglutarate/zn2+/coa (see paper)
24% identity, 76% coverage: 6:262/338 of query aligns to 21:280/399 of 6ktqA
- binding 2-oxoglutaric acid: R30 (= R15), R154 (≠ V135), T156 (≠ F137), E158 (≠ M139), S184 (≠ Y165), T188 (≠ S169), H216 (= H198), H218 (= H200)
- binding coenzyme a: V67 (≠ T66), R96 (≠ H95), A97 (≠ D96), F116 (vs. gap), H128 (≠ T112), E158 (≠ M139)
- binding zinc ion: E31 (≠ D16), H216 (= H198), H218 (= H200)
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)
23% identity, 82% coverage: 1:278/338 of query aligns to 1:287/517 of Q9JZG1
- D16 (= D16) binding
- H204 (= H198) binding
- H206 (= H200) binding
- N240 (= N234) binding
Sites not aligning to the query:
- 366:517 Required for the condensation reaction. Not required to bind substrate
O87198 Homocitrate synthase; HCS; EC 2.3.3.14 from Thermus thermophilus (strain ATCC BAA-163 / DSM 7039 / HB27) (see paper)
27% identity, 74% coverage: 9:258/338 of query aligns to 6:255/376 of O87198
- R12 (= R15) binding
- E13 (≠ D16) binding
- H72 (= H80) 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 (vs. gap) binding
- R133 (≠ S141) binding
- S135 (≠ M143) binding
- T166 (≠ S169) binding ; binding
- H195 (= H198) binding
- H197 (= H200) binding
Q8F3Q1 (R)-citramalate synthase CimA; LiCMS; EC 2.3.3.21 from Leptospira interrogans serogroup Icterohaemorrhagiae serovar Lai (strain 56601) (see 2 papers)
24% identity, 71% coverage: 4:243/338 of query aligns to 5:252/516 of Q8F3Q1
- R16 (= R15) mutation R->K,Q: Loss of activity.
- RD 16:17 (= RD 15:16) binding
- D17 (= D16) 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 (≠ A84) 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 (≠ L86) mutation to A: 5-fold increase in Km for acetyl-CoA and 120-fold decrease in kcat.
- L104 (≠ A111) mutation to V: 1.8-fold increase in Km for pyruvate and 3.4-fold decrease in kcat.
- Y144 (≠ F137) 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 (≠ S169) 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, 70% coverage: 6:243/338 of query aligns to 1:246/311 of 3bliA
3rmjB Crystal structure of truncated alpha-isopropylmalate synthase from neisseria meningitidis (see paper)
23% identity, 81% coverage: 6:278/338 of query aligns to 3:284/308 of 3rmjB
3ivsA Homocitrate synthase lys4 (see paper)
26% identity, 69% coverage: 9:242/338 of query aligns to 14:232/364 of 3ivsA
2zyfA Crystal structure of homocitrate synthase from thermus thermophilus complexed with magnesuim ion and alpha-ketoglutarate (see paper)
26% identity, 74% coverage: 9:258/338 of query aligns to 6:249/314 of 2zyfA
2ztjA Crystal structure of homocitrate synthase from thermus thermophilus complexed with alpha-ketoglutarate (see paper)
25% identity, 74% coverage: 9:258/338 of query aligns to 6:247/312 of 2ztjA
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)
25% identity, 43% coverage: 124:267/338 of query aligns to 199:353/370 of Q8TB92
- L237 (≠ M156) mutation to S: Abolishes catalytic activity.
- H278 (= H198) 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.
- 86 R→Q: Abolishes catalytic activity.
3mi3A Homocitrate synthase lys4 bound to lysine (see paper)
25% identity, 69% coverage: 9:242/338 of query aligns to 14:234/370 of 3mi3A
3a9iA Crystal structure of homocitrate synthase from thermus thermophilus complexed with lys (see paper)
26% identity, 74% coverage: 9:258/338 of query aligns to 5:248/347 of 3a9iA
3ivtB Homocitrate synthase lys4 bound to 2-og (see paper)
24% identity, 69% coverage: 9:242/338 of query aligns to 32:263/400 of 3ivtB
Query Sequence
>RR42_RS27900 FitnessBrowser__Cup4G11:RR42_RS27900
MQGQKKIYISDVTLRDGSHAVRHQYSVEQARQIAKALDDAKVDSIEVAHGDGLQGSSFNY
GFGAHTDLEWIEAVASVVKHAKIATLLLPGIGTVHDLKAAYDAGARIVRVATHCTEADVS
RQHIEYARHLGMEAVGFLMMSHMTTPQNLAAQAKLMESYGATCCYVVDSGGALTMNDVRD
RFRAFKAVLKPETQTGMHAHHNLSLGVANSIVAVEEGCDRIDASLAGMGAGAGNAPLEVF
IAAAERMGWDHGCDLYKLMDAADDIVRPLQDRPVRVDRETLALGYAGVYSSFLRHSEAAA
SKYGLKTVDVLVELGRRRMVGGQEDMIVDVALDLLKAR
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