SitesBLAST
Comparing PfGW456L13_2506 FitnessBrowser__pseudo13_GW456_L13:PfGW456L13_2506 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)
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)
74% identity, 100% coverage: 1:344/344 of query aligns to 1:344/346 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.
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)
54% identity, 96% coverage: 6:335/344 of query aligns to 7:336/345 of P51016
- D18 (= D17) binding
- H200 (= H199) binding
- H202 (= H201) binding
Sites not aligning to the query:
- 1 modified: Initiator methionine, Removed
4jn6C Crystal structure of the aldolase-dehydrogenase complex from mycobacterium tuberculosis hrv37 (see paper)
51% identity, 96% coverage: 8:337/344 of query aligns to 4:333/339 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 (≠ T168), S166 (= S170), H195 (= H199), H197 (= H201), Y286 (= Y290)
1nvmA Crystal structure of a bifunctional aldolase-dehydrogenase : sequestering a reactive and volatile intermediate (see paper)
54% identity, 96% coverage: 6:335/344 of query aligns to 6:335/340 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)
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)
51% identity, 96% coverage: 8:337/344 of query aligns to 7:336/346 of P9WMK5
- D16 (= D17) binding
- H198 (= H199) binding
- H200 (= H201) binding
- G322 (= G323) mutation to F: Abolishes substrate channeling to HsaG.
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, 94% coverage: 12:336/344 of query aligns to 15:338/347 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
48% identity, 97% coverage: 8:339/344 of query aligns to 4:335/337 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 (≠ T168), S166 (= S170), H195 (= H199), H197 (= H201), Y286 (= Y290)
2zyfA Crystal structure of homocitrate synthase from thermus thermophilus complexed with magnesuim ion and alpha-ketoglutarate (see paper)
27% identity, 69% coverage: 6:243/344 of query aligns to 2:233/314 of 2zyfA
2ztjA Crystal structure of homocitrate synthase from thermus thermophilus complexed with alpha-ketoglutarate (see paper)
27% identity, 69% coverage: 6:243/344 of query aligns to 2:231/312 of 2ztjA
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: 4:279/344 of query aligns to 3:287/517 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
O87198 Homocitrate synthase; HCS; EC 2.3.3.14 from Thermus thermophilus (strain ATCC BAA-163 / DSM 7039 / HB27) (see paper)
26% identity, 69% coverage: 6:243/344 of query aligns to 2:239/376 of O87198
- R12 (= R16) binding
- E13 (≠ D17) binding
- H72 (≠ A74) 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 (≠ D119) binding
- S135 (= S121) binding
- T166 (≠ S170) binding ; binding
- H195 (= H199) binding
- H197 (= H201) binding
3a9iA Crystal structure of homocitrate synthase from thermus thermophilus complexed with lys (see paper)
26% identity, 69% coverage: 6:243/344 of query aligns to 1:232/347 of 3a9iA
3rmjB Crystal structure of truncated alpha-isopropylmalate synthase from neisseria meningitidis (see paper)
26% identity, 79% coverage: 8:279/344 of query aligns to 4:284/308 of 3rmjB
6e1jA Crystal structure of methylthioalkylmalate synthase (bjumam1.1) from brassica juncea (see paper)
26% identity, 74% coverage: 8:260/344 of query aligns to 18:292/409 of 6e1jA
- binding coenzyme a: Q30 (≠ H20), F60 (= F63), S63 (≠ H66), I95 (= I76), R97 (≠ K78), F121 (vs. gap), K132 (≠ H97), L133 (= L98)
- binding 4-(methylsulfanyl)-2-oxobutanoic acid: P192 (≠ T168), T194 (≠ S170), H225 (= H199), H227 (= H201)
- binding manganese (ii) ion: D27 (= D17), V82 (vs. gap), E84 (vs. gap), H225 (= H199), H227 (= H201)
Sites not aligning to the query:
3bliA Crystal structure of the catalytic domain of licms in complexed with pyruvate and acetyl-coa (see paper)
36% identity, 28% coverage: 165:259/344 of query aligns to 168:260/311 of 3bliA
Sites not aligning to the query:
3ivsA Homocitrate synthase lys4 (see paper)
27% identity, 69% coverage: 14:250/344 of query aligns to 18:236/364 of 3ivsA
Q8F3Q1 (R)-citramalate synthase CimA; LiCMS; EC 2.3.3.21 from Leptospira interrogans serogroup Icterohaemorrhagiae serovar Lai (strain 56601) (see 2 papers)
36% identity, 28% coverage: 165:259/344 of query aligns to 174:266/516 of Q8F3Q1
- 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:
- 16 mutation R->K,Q: Loss of activity.
- 16:17 binding
- 17 D→A: 34-fold increase in Km for pyruvate and 315-fold decrease in kcat.; D→N: 4.4-fold increase in Km for pyruvate and 480-fold decrease in kcat.
- 81 L→A: 4.7-fold increase in Km for pyruvate and 15.7-fold decrease in kcat.; L→V: 3.3-fold increase in Km for pyruvate and 10.1-fold decrease in kcat.
- 83 F→A: 5-fold increase in Km for acetyl-CoA and 120-fold decrease in kcat.
- 104 L→V: 1.8-fold increase in Km for pyruvate and 3.4-fold decrease in kcat.
- 144 binding ; Y→L: 259-fold increase in Km for pyruvate and 76-fold decrease in kcat.; Y→V: 114-fold increase in Km for pyruvate and 5.3-fold decrease in kcat.
- 146 mutation E->D,Q: Minor effects on the binding of acetyl-CoA, but causes a strong decrease in kcat.
- 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.
6ktqA Crystal structure of catalytic domain of homocitrate synthase from sulfolobus acidocaldarius (sahcs(dram)) in complex with alpha- ketoglutarate/zn2+/coa (see paper)
34% identity, 33% coverage: 150:263/344 of query aligns to 168:280/399 of 6ktqA
Sites not aligning to the query:
2nx9B Crystal structure of the carboxyltransferase domain of the oxaloacetate decarboxylase na+ pump from vibrio cholerae (see paper)
24% identity, 75% coverage: 6:263/344 of query aligns to 5:270/453 of 2nx9B
Sites not aligning to the query:
3mi3A Homocitrate synthase lys4 bound to lysine (see paper)
27% identity, 69% coverage: 14:250/344 of query aligns to 18:238/370 of 3mi3A
Query Sequence
>PfGW456L13_2506 FitnessBrowser__pseudo13_GW456_L13:PfGW456L13_2506
MNLQGKSVRLHDMSLRDGMHAKQHQISIEQMVSVATGLDAAGVPLIEITHGDGLGGASLN
YGFPAHSDEEYFSAVIPKMKQAKVSALLLPGIGTLDHLKMAHEHGVSTIRVATHCTEADV
SGQHIGMSAKMGLDTVGFLMMAHMVSPEKLLEQARLMESYGANCIYCTDSAGYMLPDEVT
QKIGALRAGLNAGTEVGFHGHHNMGMAIANSLAAIEAGAARIDGSVAGLGAGAGNTPLEV
FVAVLERMGVNSGVDLYKIMDVAEDLVVPMMDQPIRLDRDALTLGYAGVYSSFLLFAKRA
EQKYGIAARELLVELGRRGTVGGQEDMIEDLALTLSRARGVLPT
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