SitesBLAST
Comparing BPHYT_RS07250 FitnessBrowser__BFirm:BPHYT_RS07250 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)
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)
76% identity, 97% coverage: 3:340/347 of query aligns to 4:341/345 of P51016
- D18 (= D17) binding
- H200 (= H199) binding
- H202 (= H201) 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)
76% identity, 97% coverage: 3:340/347 of query aligns to 3:340/340 of 1nvmA
- active site: D17 (= D17), H20 (= H20), H199 (= H199), H201 (= H201), Y290 (= Y290)
- binding manganese (ii) ion: D17 (= D17), H199 (= H199), H201 (= H201)
- binding oxalate ion: R16 (= R16), F138 (= F138), M140 (= M140), S170 (= S170), H199 (= H199), H201 (= H201), Y290 (= Y290)
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, 98% coverage: 1:341/347 of query aligns to 1:341/346 of P51015
- R16 (= R16) mutation to A: Loss of aldol cleavage activity.; mutation to K: 4000-fold decrease in the catalytic efficiency of the aldol cleavage reaction.
- H20 (= H20) 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 (= L87) 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 (= L89) 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 (= Y290) 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 (= G322) 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 (= G323) 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)
54% identity, 97% coverage: 4:340/347 of query aligns to 7:341/347 of Q53WI0
- A324 (≠ G322) 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
51% identity, 96% coverage: 6:339/347 of query aligns to 2:335/337 of 4lrsA
- active site: D13 (= D17), H16 (= H20), H195 (= H199), H197 (= H201), Y286 (= Y290)
- binding magnesium ion: D13 (= D17), H195 (= H199), H197 (= H201)
- binding pyruvic acid: R12 (= R16), D13 (= D17), F134 (= F138), M136 (= M140), V164 (= V168), S166 (= S170), H195 (= H199), H197 (= H201), Y286 (= Y290)
4jn6C Crystal structure of the aldolase-dehydrogenase complex from mycobacterium tuberculosis hrv37 (see paper)
50% identity, 96% coverage: 8:341/347 of query aligns to 4:335/339 of 4jn6C
- active site: D13 (= D17), H16 (= H20), H195 (= H199), H197 (= H201), Y286 (= Y290)
- binding manganese (ii) ion: D13 (= D17), H195 (= H199), H197 (= H201)
- binding oxalate ion: R12 (= R16), M136 (= M140), V164 (= V168), S166 (= S170), H195 (= H199), H197 (= H201), Y286 (= Y290)
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, 98% coverage: 1:341/347 of query aligns to 1:338/346 of P9WMK5
- D16 (= D17) binding
- H198 (= H199) binding
- H200 (= H201) binding
- G322 (= G323) mutation to F: Abolishes substrate channeling to HsaG.
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)
26% identity, 80% coverage: 1:279/347 of query aligns to 1:287/517 of Q9JZG1
- D16 (= D17) binding
- H204 (= H199) binding
- H206 (= H201) binding
- N240 (= N235) 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)
25% identity, 79% coverage: 5:279/347 of query aligns to 1:284/308 of 3rmjB
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, 71% coverage: 1:245/347 of query aligns to 1:253/516 of Q8F3Q1
- R16 (= R16) mutation R->K,Q: Loss of activity.
- RD 16:17 (= RD 16:17) binding
- D17 (= D17) 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 (= L88) 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 (≠ A112) mutation to V: 1.8-fold increase in Km for pyruvate and 3.4-fold decrease in kcat.
- Y144 (≠ F138) 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 (≠ S170) 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, 69% coverage: 7:245/347 of query aligns to 1:247/311 of 3bliA
Q9FG67 Methylthioalkylmalate synthase 1, chloroplastic; 2-isopropylmalate synthase 3; EC 2.3.3.17 from Arabidopsis thaliana (Mouse-ear cress) (see paper)
26% identity, 69% coverage: 8:245/347 of query aligns to 85:338/506 of Q9FG67
- S102 (≠ Q25) mutation to F: In gsm1-1; loss of conversion of C3 to C4 glucosinolates.
- A290 (≠ G197) 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)
28% identity, 67% coverage: 10:243/347 of query aligns to 6:239/376 of O87198
- R12 (= R16) binding
- E13 (≠ D17) binding
- H72 (= H66) 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 (≠ T86) binding
- R133 (≠ G137) binding
- S135 (≠ L139) binding
- T166 (≠ N175) binding ; binding
- H195 (= H199) binding
- H197 (= H201) binding
6e1jA Crystal structure of methylthioalkylmalate synthase (bjumam1.1) from brassica juncea (see paper)
23% identity, 71% coverage: 1:245/347 of query aligns to 12:271/409 of 6e1jA
- binding coenzyme a: Q30 (≠ H20), F60 (≠ Y61), S63 (≠ G64), I95 (≠ V95), R97 (vs. gap), F121 (≠ H114), K132 (vs. gap), L133 (vs. gap)
- binding 4-(methylsulfanyl)-2-oxobutanoic acid: P192 (≠ V168), T194 (≠ S170), H225 (= H199), H227 (= H201)
- binding manganese (ii) ion: D27 (= D17), V82 (≠ A82), E84 (≠ V84), H225 (= H199), H227 (= H201)
Sites not aligning to the query:
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)
23% identity, 69% coverage: 8:245/347 of query aligns to 85:338/503 of Q9FN52
- G263 (≠ A173) 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)
24% identity, 76% coverage: 7:269/347 of query aligns to 21:292/399 of 6ktqA
- binding 2-oxoglutaric acid: R30 (= R16), R154 (≠ V136), T156 (≠ F138), E158 (≠ M140), S184 (≠ Y166), T188 (≠ S170), H216 (= H199), H218 (= H201)
- binding coenzyme a: V67 (vs. gap), R96 (≠ F63), A97 (≠ G64), F116 (≠ L89), H128 (≠ Y102), E158 (≠ M140)
- binding zinc ion: E31 (≠ D17), H216 (= H199), H218 (= H201)
3ivsA Homocitrate synthase lys4 (see paper)
23% identity, 71% coverage: 14:259/347 of query aligns to 18:251/364 of 3ivsA
3mi3A Homocitrate synthase lys4 bound to lysine (see paper)
23% identity, 71% coverage: 14:259/347 of query aligns to 18:253/370 of 3mi3A
P35914 Hydroxymethylglutaryl-CoA lyase, mitochondrial; HL; HMG-CoA lyase; 3-hydroxy-3-methylglutarate-CoA lyase; EC 4.1.3.4 from Homo sapiens (Human) (see 11 papers)
21% identity, 77% coverage: 6:273/347 of query aligns to 31:313/325 of P35914
- E37 (≠ D12) to K: in HMGCLD; activity lower than 5% respect to the wild-type; mutation to D: Normal activity.
- R41 (= R16) to Q: in HMGCLD; loss of activity and of proton exchange; dbSNP:rs121964997; mutation to M: Reduced activity, and loss of proton exchange.
- D42 (= D17) to E: in HMGCLD; reduced activity; to G: in HMGCLD; loss of activity; dbSNP:rs1467902610; to H: in HMGCLD; loss of activity; mutation D->A,N: Loss of activity, and reduced proton exchange rate.
- K48 (≠ R23) to N: in HMGCLD; abolishes almost all enzymatic activity
- E72 (= E47) mutation to A: Loss of activity, and reduced affinity for metal cofactor and substrate.
- S142 (vs. gap) to F: in HMGCLD; activity lower than 5% respect to the wild-type
- C174 (≠ T145) to Y: in HMGCLD; activity lower than 5% respect to the wild-type; dbSNP:rs765475941
- F192 (≠ Y160) to S: in HMGCLD; activity lower than 5% respect to the wild-type
- I200 (≠ V168) to F: in HMGCLD; activity lower than 5% respect to the wild-type
- G203 (= G171) to E: in HMGCLD; complete loss of activity; dbSNP:rs1553131940
- D204 (≠ V172) mutation to A: Reduced activity, and reduced affinity for metal cofactor and substrate.
- H233 (= H199) to R: in HMGCLD; loss of activity; dbSNP:rs727503963; mutation to A: Loss of activity, and reduced proton exchange rate.
- E279 (= E239) mutation to A: Reduced thermal stability, but normal activity.
- D280 (≠ V240) mutation to A: Normal activity.
Sites not aligning to the query:
- 323 modified: Interchain; C→S: Abolishes interchain homodimerization. Exhibits no DTT stimulated activity.
3mp3B Crystal structure of human lyase in complex with inhibitor hg-coa (see paper)
21% identity, 77% coverage: 6:273/347 of query aligns to 4:286/296 of 3mp3B
- binding (3R,5S,9R,21S)-1-[(2R,3S,4R,5R)-5-(6-amino-9H-purin-9-yl)-4-hydroxy-3-(phosphonooxy)tetrahydrofuran-2-yl]-3,5,9,21-tetrahydroxy-8,8-dimethyl-10,14,19-trioxo-2,4,6-trioxa-18-thia-11,15-diaza-3,5-diphosphatricosan-23-oic acid 3,5-dioxide: R14 (= R16), D15 (= D17), Q18 (≠ H20), F49 (≠ L54), V50 (≠ A55), S51 (≠ G56), W54 (≠ F59), P81 (vs. gap), N82 (≠ T94), K84 (≠ H96), G85 (≠ D97), N111 (≠ H124), R122 (vs. gap), Y140 (≠ F138), S142 (≠ M140), T178 (≠ A173), H206 (= H199)
- binding magnesium ion: D15 (= D17), H206 (= H199), H208 (= H201)
Query Sequence
>BPHYT_RS07250 FitnessBrowser__BFirm:BPHYT_RS07250
MTDSNKKIYVSDVTLRDGMHAIRHQYSLQSAVAIAQALDEAGVDSIEVAHGDGLAGSSFN
YGFGAHTDLEWIEAVAATVKRAQVATLLLPGIGTVHDLRAAYDAGARVVRIATHCTEADI
SKQHIEYARSLGMDTVGFLMMSHMTSPEALAKQAKLMESYGAQCVYVVDSGVALNMRDVA
ERFDAFKAVLDPATQTGMHAHHNLSLGVANSIVALEHGCDRVDASLTGMGAGAGNAPLEV
FIAAVDRMKLKHGCDVKQLIDAAEDIVRPLQERPVRVDRETLALGYAGVYSSFLRHTEAA
AAKYGLSAFDIMVELGKRRMVGGQEDMIVDVALDMLKARELANQEAA
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