SitesBLAST
Comparing RR42_RS05095 FitnessBrowser__Cup4G11:RR42_RS05095 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)
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)
77% identity, 99% coverage: 2:332/335 of query aligns to 7:337/345 of P51016
- D18 (= D13) binding
- H200 (= H195) binding
- H202 (= H197) binding
Sites not aligning to the query:
- 1 modified: Initiator methionine, Removed
1nvmA Crystal structure of a bifunctional aldolase-dehydrogenase : sequestering a reactive and volatile intermediate (see paper)
77% identity, 99% coverage: 2:332/335 of query aligns to 6:336/340 of 1nvmA
- active site: D17 (= D13), H20 (= H16), H199 (= H195), H201 (= H197), Y290 (= Y286)
- binding manganese (ii) ion: D17 (= D13), H199 (= H195), H201 (= H197)
- binding oxalate ion: R16 (= R12), F138 (= F134), M140 (= M136), S170 (= S166), H199 (= H195), H201 (= H197), Y290 (= Y286)
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)
59% identity, 100% coverage: 2:335/335 of query aligns to 6:339/346 of P51015
- R16 (= R12) mutation to A: Loss of aldol cleavage activity.; mutation to K: 4000-fold decrease in the catalytic efficiency of the aldol cleavage reaction.
- H20 (= H16) 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 (= L83) 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 (= L85) 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 (= Y286) 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 (= G318) 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 (= G319) 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.
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
51% identity, 100% coverage: 2:335/335 of query aligns to 2:335/337 of 4lrsA
- active site: D13 (= D13), H16 (= H16), H195 (= H195), H197 (= H197), Y286 (= Y286)
- binding magnesium ion: D13 (= D13), H195 (= H195), H197 (= H197)
- binding pyruvic acid: R12 (= R12), D13 (= D13), F134 (= F134), M136 (= M136), V164 (= V164), S166 (= S166), H195 (= H195), H197 (= H197), Y286 (= Y286)
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)
53% identity, 99% coverage: 2:331/335 of query aligns to 9:337/347 of Q53WI0
- A324 (≠ G318) mutation to G: Increases the channeling efficiency of propanaldehyde from 57% to 94%.
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, 100% coverage: 1:334/335 of query aligns to 4:337/346 of P9WMK5
- D16 (= D13) binding
- H198 (= H195) binding
- H200 (= H197) binding
- G322 (= G319) mutation to F: Abolishes substrate channeling to HsaG.
4jn6C Crystal structure of the aldolase-dehydrogenase complex from mycobacterium tuberculosis hrv37 (see paper)
50% identity, 100% coverage: 1:334/335 of query aligns to 1:334/339 of 4jn6C
- active site: D13 (= D13), H16 (= H16), H195 (= H195), H197 (= H197), Y286 (= Y286)
- binding manganese (ii) ion: D13 (= D13), H195 (= H195), H197 (= H197)
- binding oxalate ion: R12 (= R12), M136 (= M136), V164 (= V164), S166 (= S166), H195 (= H195), H197 (= H197), Y286 (= Y286)
3bliA Crystal structure of the catalytic domain of licms in complexed with pyruvate and acetyl-coa (see paper)
25% identity, 77% coverage: 3:259/335 of query aligns to 1:266/311 of 3bliA
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, 77% coverage: 3:259/335 of query aligns to 7:272/516 of Q8F3Q1
- R16 (= R12) mutation R->K,Q: Loss of activity.
- RD 16:17 (= RD 12:13) binding
- D17 (= D13) 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 (= L83) 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 (≠ L84) mutation to A: 5-fold increase in Km for acetyl-CoA and 120-fold decrease in kcat.
- L104 (≠ A108) mutation to V: 1.8-fold increase in Km for pyruvate and 3.4-fold decrease in kcat.
- Y144 (≠ F134) 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 (≠ S166) 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.
3rmjB Crystal structure of truncated alpha-isopropylmalate synthase from neisseria meningitidis (see paper)
25% identity, 81% coverage: 3:275/335 of query aligns to 3:284/308 of 3rmjB
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, 81% coverage: 3:275/335 of query aligns to 6:287/517 of Q9JZG1
- D16 (= D13) binding
- H204 (= H195) binding
- H206 (= H197) binding
- N240 (= N231) 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, 72% coverage: 4:245/335 of query aligns to 85:342/506 of Q9FG67
- S102 (≠ Q21) mutation to F: In gsm1-1; loss of conversion of C3 to C4 glucosinolates.
- A290 (≠ G193) mutation to T: In gsm1-2; loss of conversion of C3 to C4 glucosinolates.
O87198 Homocitrate synthase; HCS; EC 2.3.3.14 from Thermus thermophilus (strain ATCC BAA-163 / DSM 7039 / HB27) (see paper)
25% identity, 71% coverage: 1:239/335 of query aligns to 1:239/376 of O87198
- R12 (= R12) binding
- E13 (≠ D13) binding
- H72 (≠ A70) 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 (≠ S138) binding
- S135 (≠ M140) binding
- T166 (≠ S166) binding ; binding
- H195 (= H195) binding
- H197 (= H197) binding
3ivsA Homocitrate synthase lys4 (see paper)
25% identity, 73% coverage: 10:255/335 of query aligns to 18:251/364 of 3ivsA
3mi3A Homocitrate synthase lys4 bound to lysine (see paper)
24% identity, 73% coverage: 10:255/335 of query aligns to 18:253/370 of 3mi3A
2zyfA Crystal structure of homocitrate synthase from thermus thermophilus complexed with magnesuim ion and alpha-ketoglutarate (see paper)
24% identity, 71% coverage: 1:239/335 of query aligns to 1:233/314 of 2zyfA
6ktqA Crystal structure of catalytic domain of homocitrate synthase from sulfolobus acidocaldarius (sahcs(dram)) in complex with alpha- ketoglutarate/zn2+/coa (see paper)
26% identity, 71% coverage: 3:241/335 of query aligns to 21:262/399 of 6ktqA
- binding 2-oxoglutaric acid: R30 (= R12), R154 (≠ V132), T156 (≠ F134), E158 (≠ M136), S184 (≠ Y162), T188 (≠ S166), H216 (= H195), H218 (= H197)
- binding coenzyme a: V67 (vs. gap), R96 (≠ F59), A97 (≠ G60), F116 (≠ L85), H128 (≠ Y98), E158 (≠ M136)
- binding zinc ion: E31 (≠ D13), H216 (= H195), H218 (= H197)
Q9Y823 Homocitrate synthase, mitochondrial; HCS; EC 2.3.3.14 from Schizosaccharomyces pombe (strain 972 / ATCC 24843) (Fission yeast) (see 2 papers)
25% identity, 73% coverage: 10:255/335 of query aligns to 41:287/418 of Q9Y823
- R43 (= R12) binding ; mutation R->A,K,Q: Abolishes the catalytic activity.
- E44 (≠ D13) binding ; binding ; binding
- Q47 (≠ H16) mutation to A: Abolishes the catalytic activity.
- E74 (= E43) 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 (vs. gap) binding ; mutation to A: Substantially impairs catalytic efficiency.
- D123 (vs. gap) binding ; mutation to N: Does not affect the catalytic activity but impairs L-lysine inhibition.
- R163 (≠ V132) binding ; mutation R->A,Q: Abolishes the catalytic activity.; mutation to K: Severely diminishes affinity for 2-oxoglutarate and substantially impairs catalytic efficiency.
- S165 (≠ F134) binding ; mutation to A: Results in a moderate decrease in catalytic efficiency.
- E167 (≠ M136) mutation E->A,Q: Abolishes the catalytic activity.
- T197 (≠ S166) 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 (= E191) mutation to Q: Does not affect the catalytic activity but impairs L-lysine inhibition.
- H224 (= H195) binding ; binding
- H226 (= H197) binding ; binding
Sites not aligning to the query:
- 288 R→K: Does not affect the catalytic activity but impairs L-lysine inhibition.
- 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.
2ztjA Crystal structure of homocitrate synthase from thermus thermophilus complexed with alpha-ketoglutarate (see paper)
24% identity, 71% coverage: 1:239/335 of query aligns to 1:231/312 of 2ztjA
3ivtB Homocitrate synthase lys4 bound to 2-og (see paper)
25% identity, 73% coverage: 10:255/335 of query aligns to 36:282/400 of 3ivtB
Query Sequence
>RR42_RS05095 FitnessBrowser__Cup4G11:RR42_RS05095
MKKVHVSDVTLRDGMHAIRHQYSLPQAVAIARALDAARVDSIEVAHGDGLNGSSFNYGFG
AHTDLEWIAAVAAQLKHARVATLLLPGIGTIHDLRAAYDAGARTVRVATHCTEADISRQH
IEYARKLGMDTVGFLMMSHMTTPAALAQQARLMESYGAQCVYVVDSGGALSMRDVAERFD
AFKQVLDPATETGMHAHHNLSLGVANSMVALEHGCDRVDASLAGMGAGAGNAPLEVFIAA
IDRAGIAHGTDLHALMDAADDLVRPLQDRPVRVDRETLALGYAGVYSSFLRHAEAASARY
GIATVDILVELGRRRMVGGQEDMIVDVALDLLRQR
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