SitesBLAST
Comparing SM_b21125 FitnessBrowser__Smeli:SM_b21125 to proteins with known functional sites using BLASTp with E ≤ 0.001.
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Found 15 hits to proteins with known functional sites (download)
1ydnA Crystal structure of the hmg-coa lyase from brucella melitensis, northeast structural genomics target lr35. (see paper)
63% identity, 97% coverage: 7:287/289 of query aligns to 2:282/283 of 1ydnA
3mp3B Crystal structure of human lyase in complex with inhibitor hg-coa (see paper)
53% identity, 95% coverage: 7:281/289 of query aligns to 4:278/296 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 (= R17), D15 (= D18), Q18 (= Q21), F49 (= F52), V50 (= V53), S51 (= S54), W54 (= W57), P81 (= P84), N82 (= N85), K84 (≠ R87), G85 (= G88), N111 (= N114), R122 (= R125), Y140 (= Y143), S142 (= S145), T178 (= T181), H206 (= H209)
- binding magnesium ion: D15 (= D18), H206 (= H209), H208 (= H211)
2cw6A Crystal structure of human hmg-coa lyase: insights into catalysis and the molecular basis for hydroxymethylglutaric aciduria (see paper)
53% identity, 95% coverage: 7:281/289 of query aligns to 4:278/296 of 2cw6A
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)
53% identity, 95% coverage: 7:281/289 of query aligns to 31:305/325 of P35914
- E37 (= E13) to K: in HMGCLD; activity lower than 5% respect to the wild-type; mutation to D: Normal activity.
- R41 (= R17) to Q: in HMGCLD; loss of activity and of proton exchange; dbSNP:rs121964997; mutation to M: Reduced activity, and loss of proton exchange.
- D42 (= D18) 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 (≠ S24) to N: in HMGCLD; abolishes almost all enzymatic activity
- E72 (= E48) mutation to A: Loss of activity, and reduced affinity for metal cofactor and substrate.
- S142 (= S118) to F: in HMGCLD; activity lower than 5% respect to the wild-type
- C174 (= C150) to Y: in HMGCLD; activity lower than 5% respect to the wild-type; dbSNP:rs765475941
- F192 (≠ L168) to S: in HMGCLD; activity lower than 5% respect to the wild-type
- I200 (= I176) to F: in HMGCLD; activity lower than 5% respect to the wild-type
- G203 (= G179) to E: in HMGCLD; complete loss of activity; dbSNP:rs1553131940
- D204 (= D180) mutation to A: Reduced activity, and reduced affinity for metal cofactor and substrate.
- H233 (= H209) to R: in HMGCLD; loss of activity; dbSNP:rs727503963; mutation to A: Loss of activity, and reduced proton exchange rate.
- E279 (≠ L255) mutation to A: Reduced thermal stability, but normal activity.
- D280 (≠ A256) mutation to A: Normal activity.
Sites not aligning to the query:
- 323 modified: Interchain; C→S: Abolishes interchain homodimerization. Exhibits no DTT stimulated activity.
3mp5B Crystal structure of human lyase r41m in complex with hmg-coa (see paper)
52% identity, 95% coverage: 7:281/289 of query aligns to 4:278/296 of 3mp5B
- binding 3-hydroxy-3-methylglutaryl-coenzyme a: D15 (= D18), Q18 (= Q21), S51 (= S54), W54 (= W57), F100 (= F103), N111 (= N114), N113 (= N116), Y140 (= Y143), S142 (= S145), T178 (= T181), C239 (= C242)
- binding magnesium ion: D15 (= D18), H206 (= H209), H208 (= H211)
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)
53% identity, 95% coverage: 7:281/289 of query aligns to 76:350/370 of Q8TB92
- R86 (= R17) mutation to Q: Abolishes catalytic activity.
- L237 (= L168) mutation to S: Abolishes catalytic activity.
- H278 (= H209) 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.
P13703 Hydroxymethylglutaryl-CoA lyase; HL; HMG-CoA lyase; 3-hydroxy-3-methylglutarate-CoA lyase; EC 4.1.3.4 from Pseudomonas mevalonii (see paper)
50% identity, 93% coverage: 7:275/289 of query aligns to 2:270/301 of P13703
- C237 (= C242) active site
6ndsA Structure of an hmg-coa lyase from acenitobacter baumannii in complex with coenzyme a and 3-methylmalate
37% identity, 96% coverage: 9:285/289 of query aligns to 8:280/305 of 6ndsA
- binding coenzyme a: V52 (= V53), S53 (= S54), I57 (≠ V58), N84 (= N85), G87 (= G88), R90 (≠ A91), N113 (= N114), M114 (≠ I115), R115 (≠ N116)
- binding zinc ion: D17 (= D18), H207 (= H209), H209 (= H211)
2nx9B Crystal structure of the carboxyltransferase domain of the oxaloacetate decarboxylase na+ pump from vibrio cholerae (see paper)
31% identity, 43% coverage: 164:287/289 of query aligns to 162:278/453 of 2nx9B
Sites not aligning to the query:
Q9Y823 Homocitrate synthase, mitochondrial; HCS; EC 2.3.3.14 from Schizosaccharomyces pombe (strain 972 / ATCC 24843) (Fission yeast) (see 2 papers)
24% identity, 80% coverage: 10:240/289 of query aligns to 36:255/418 of Q9Y823
- R43 (= R17) binding ; mutation R->A,K,Q: Abolishes the catalytic activity.
- E44 (≠ D18) binding ; binding ; binding
- Q47 (= Q21) mutation to A: Abolishes the catalytic activity.
- E74 (= E48) 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 (≠ P84) binding ; mutation to A: Substantially impairs catalytic efficiency.
- D123 (≠ A101) binding ; mutation to N: Does not affect the catalytic activity but impairs L-lysine inhibition.
- R163 (= R141) binding ; mutation R->A,Q: Abolishes the catalytic activity.; mutation to K: Severely diminishes affinity for 2-oxoglutarate and substantially impairs catalytic efficiency.
- S165 (≠ V144) binding ; mutation to A: Results in a moderate decrease in catalytic efficiency.
- E167 (= E149) mutation E->A,Q: Abolishes the catalytic activity.
- T197 (= T181) 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 (≠ A207) mutation to Q: Does not affect the catalytic activity but impairs L-lysine inhibition.
- H224 (= H209) binding ; binding
- H226 (= H211) 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.
3ivtB Homocitrate synthase lys4 bound to 2-og (see paper)
24% identity, 80% coverage: 10:240/289 of query aligns to 31:250/400 of 3ivtB
3mi3A Homocitrate synthase lys4 bound to lysine (see paper)
25% identity, 80% coverage: 10:240/289 of query aligns to 13:221/370 of 3mi3A
5ks8C Crystal structure of two-subunit pyruvate carboxylase from methylobacillus flagellatus (see paper)
26% identity, 97% coverage: 8:287/289 of query aligns to 1:273/603 of 5ks8C
- active site: D11 (= D18), D115 (≠ A104), K172 (≠ G179), H201 (= H209), H203 (= H211)
- binding manganese (ii) ion: D11 (= D18), K172 (≠ G179), H201 (= H209), H203 (= H211)
- binding pyruvic acid: L79 (= L82), R81 (vs. gap), F114 (= F103), M174 (≠ T181)
5ks8D Crystal structure of two-subunit pyruvate carboxylase from methylobacillus flagellatus (see paper)
26% identity, 97% coverage: 8:287/289 of query aligns to 2:274/580 of 5ks8D
- active site: D12 (= D18), D116 (≠ A104), K173 (≠ G179), H202 (= H209), H204 (= H211)
- binding 5-(hexahydro-2-oxo-1h-thieno[3,4-d]imidazol-6-yl)pentanal: D51 (vs. gap), Y56 (≠ Q60)
- binding manganese (ii) ion: D12 (= D18), K173 (≠ G179), H202 (= H209), H204 (= H211)
- binding pyruvic acid: Q15 (= Q21), G47 (vs. gap), L80 (= L82), R82 (vs. gap)
Sites not aligning to the query:
6ktqA Crystal structure of catalytic domain of homocitrate synthase from sulfolobus acidocaldarius (sahcs(dram)) in complex with alpha- ketoglutarate/zn2+/coa (see paper)
21% identity, 81% coverage: 8:240/289 of query aligns to 21:247/399 of 6ktqA
- binding 2-oxoglutaric acid: R30 (= R17), R154 (= R141), T156 (≠ Y143), E158 (≠ S145), S184 (= S177), T188 (= T181), H216 (= H209), H218 (= H211)
- binding coenzyme a: V67 (≠ D63), R96 (= R87), A97 (≠ G88), F116 (= F103), H128 (≠ I115), E158 (≠ S145)
- binding zinc ion: E31 (≠ D18), H216 (= H209), H218 (= H211)
Query Sequence
>SM_b21125 FitnessBrowser__Smeli:SM_b21125
MTSPAKERVTIVEVAPRDGLQNESRLVATEDKIRLVDLLADCGYERIEVTSFVSPRWVPQ
LADAPAVMAGIVRRPGTRYAALTPNMRGFEAALAAGADEVAIFASASESFSERNINCSIA
ESIERFRPVAEASRHRGVPLRGYVSCVVECPYEGAIVPAETARVARLLADLGCYEISLGD
TIGRGTPEAVDAMLAAALREIDAPKLAGHFHDTSGRALENIAVALERGIRVFDASAGGLG
GCPYAPGAAGNVDTLAVNAFLEAQSFATGLDSEKLDRAAAFARSLRSTA
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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