SitesBLAST
Comparing 5210130 FitnessBrowser__PV4:5210130 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)
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)
62% identity, 99% coverage: 2:298/301 of query aligns to 24:321/325 of P35914
- E37 (= E15) to K: in HMGCLD; activity lower than 5% respect to the wild-type; mutation to D: Normal activity.
- R41 (= R19) to Q: in HMGCLD; loss of activity and of proton exchange; dbSNP:rs121964997; mutation to M: Reduced activity, and loss of proton exchange.
- D42 (= D20) 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 (= K26) to N: in HMGCLD; abolishes almost all enzymatic activity
- E72 (= E49) mutation to A: Loss of activity, and reduced affinity for metal cofactor and substrate.
- S142 (= S119) to F: in HMGCLD; activity lower than 5% respect to the wild-type
- C174 (= C151) to Y: in HMGCLD; activity lower than 5% respect to the wild-type; dbSNP:rs765475941
- F192 (≠ L169) to S: in HMGCLD; activity lower than 5% respect to the wild-type
- I200 (= I177) to F: in HMGCLD; activity lower than 5% respect to the wild-type
- G203 (= G180) to E: in HMGCLD; complete loss of activity; dbSNP:rs1553131940
- D204 (= D181) mutation to A: Reduced activity, and reduced affinity for metal cofactor and substrate.
- H233 (= H210) to R: in HMGCLD; loss of activity; dbSNP:rs727503963; mutation to A: Loss of activity, and reduced proton exchange rate.
- E279 (= E256) mutation to A: Reduced thermal stability, but normal activity.
- D280 (= D257) 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)
63% identity, 97% coverage: 6:298/301 of query aligns to 1:294/296 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 (= R19), D15 (= D20), Q18 (= Q23), F49 (= F53), V50 (= V54), S51 (= S55), W54 (= W58), P81 (= P85), N82 (= N86), K84 (= K88), G85 (= G89), N111 (= N115), R122 (= R126), Y140 (= Y144), S142 (= S146), T178 (= T182), H206 (= H210)
- binding magnesium ion: D15 (= D20), H206 (= H210), H208 (= H212)
2cw6A Crystal structure of human hmg-coa lyase: insights into catalysis and the molecular basis for hydroxymethylglutaric aciduria (see paper)
63% identity, 97% coverage: 6:298/301 of query aligns to 1:294/296 of 2cw6A
3mp5B Crystal structure of human lyase r41m in complex with hmg-coa (see paper)
63% identity, 97% coverage: 6:298/301 of query aligns to 1:294/296 of 3mp5B
- binding 3-hydroxy-3-methylglutaryl-coenzyme a: D15 (= D20), Q18 (= Q23), S51 (= S55), W54 (= W58), F100 (= F104), N111 (= N115), N113 (= N117), Y140 (= Y144), S142 (= S146), T178 (= T182), C239 (= C243)
- binding magnesium ion: D15 (= D20), H206 (= H210), H208 (= H212)
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)
57% identity, 97% coverage: 8:298/301 of query aligns to 75:366/370 of Q8TB92
- R86 (= R19) mutation to Q: Abolishes catalytic activity.
- L237 (= L169) mutation to S: Abolishes catalytic activity.
- H278 (= H210) 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)
57% identity, 96% coverage: 11:299/301 of query aligns to 4:293/301 of P13703
- C237 (= C243) active site
1ydnA Crystal structure of the hmg-coa lyase from brucella melitensis, northeast structural genomics target lr35. (see paper)
55% identity, 92% coverage: 10:287/301 of query aligns to 3:280/283 of 1ydnA
6ndsA Structure of an hmg-coa lyase from acenitobacter baumannii in complex with coenzyme a and 3-methylmalate
41% identity, 94% coverage: 15:298/301 of query aligns to 12:295/305 of 6ndsA
- binding coenzyme a: V52 (= V54), S53 (= S55), I57 (≠ V59), N84 (= N86), G87 (= G89), R90 (≠ L92), N113 (= N115), M114 (≠ I116), R115 (≠ N117)
- binding zinc ion: D17 (= D20), H207 (= H210), H209 (= H212)
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, 77% coverage: 10:241/301 of query aligns to 21:247/399 of 6ktqA
- binding 2-oxoglutaric acid: R30 (= R19), R154 (= R142), T156 (≠ Y144), E158 (≠ S146), S184 (= S178), T188 (= T182), H216 (= H210), H218 (= H212)
- binding coenzyme a: V67 (≠ W58), R96 (≠ K88), A97 (≠ G89), F116 (= F104), H128 (≠ I116), E158 (≠ S146)
- binding zinc ion: E31 (≠ D20), H216 (= H210), H218 (= H212)
2nx9B Crystal structure of the carboxyltransferase domain of the oxaloacetate decarboxylase na+ pump from vibrio cholerae (see paper)
37% identity, 37% coverage: 165:276/301 of query aligns to 162:266/453 of 2nx9B
Sites not aligning to the query:
2zyfA Crystal structure of homocitrate synthase from thermus thermophilus complexed with magnesuim ion and alpha-ketoglutarate (see paper)
27% identity, 76% coverage: 12:241/301 of query aligns to 5:220/314 of 2zyfA
O87198 Homocitrate synthase; HCS; EC 2.3.3.14 from Thermus thermophilus (strain ATCC BAA-163 / DSM 7039 / HB27) (see paper)
27% identity, 76% coverage: 12:241/301 of query aligns to 5:226/376 of O87198
- R12 (= R19) binding
- E13 (≠ D20) binding
- H72 (≠ A82) 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 (≠ A102) binding
- R133 (= R142) binding
- S135 (≠ Y144) binding
- T166 (= T182) binding ; binding
- H195 (= H210) binding
- H197 (= H212) binding
2ztjA Crystal structure of homocitrate synthase from thermus thermophilus complexed with alpha-ketoglutarate (see paper)
27% identity, 76% coverage: 12:241/301 of query aligns to 5:218/312 of 2ztjA
3a9iA Crystal structure of homocitrate synthase from thermus thermophilus complexed with lys (see paper)
27% identity, 76% coverage: 12:241/301 of query aligns to 4:219/347 of 3a9iA
3rmjB Crystal structure of truncated alpha-isopropylmalate synthase from neisseria meningitidis (see paper)
24% identity, 93% coverage: 9:288/301 of query aligns to 2:277/308 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)
24% identity, 96% coverage: 1:288/301 of query aligns to 1:280/517 of Q9JZG1
- D16 (= D20) binding
- H204 (= H210) binding
- H206 (= H212) binding
- N240 (= N252) binding
Sites not aligning to the query:
- 366:517 Required for the condensation reaction. Not required to bind substrate
5ks8C Crystal structure of two-subunit pyruvate carboxylase from methylobacillus flagellatus (see paper)
27% identity, 89% coverage: 10:276/301 of query aligns to 1:261/603 of 5ks8C
- active site: D11 (= D20), D115 (≠ G105), K172 (≠ G180), H201 (= H210), H203 (= H212)
- binding manganese (ii) ion: D11 (= D20), K172 (≠ G180), H201 (= H210), H203 (= H212)
- binding pyruvic acid: L79 (≠ N86), R81 (≠ K88), F114 (= F104), M174 (≠ T182)
5ks8D Crystal structure of two-subunit pyruvate carboxylase from methylobacillus flagellatus (see paper)
27% identity, 89% coverage: 9:276/301 of query aligns to 1:262/580 of 5ks8D
- active site: D12 (= D20), D116 (≠ G105), K173 (≠ G180), H202 (= H210), H204 (= H212)
- binding 5-(hexahydro-2-oxo-1h-thieno[3,4-d]imidazol-6-yl)pentanal: D51 (= D64), Y56 (vs. gap)
- binding manganese (ii) ion: D12 (= D20), K173 (≠ G180), H202 (= H210), H204 (= H212)
- binding pyruvic acid: Q15 (= Q23), G47 (≠ P60), L80 (≠ N86), R82 (≠ K88)
Sites not aligning to the query:
3ivtB Homocitrate synthase lys4 bound to 2-og (see paper)
23% identity, 77% coverage: 9:241/301 of query aligns to 28:250/400 of 3ivtB
Q9Y823 Homocitrate synthase, mitochondrial; HCS; EC 2.3.3.14 from Schizosaccharomyces pombe (strain 972 / ATCC 24843) (Fission yeast) (see 2 papers)
23% identity, 77% coverage: 9:241/301 of query aligns to 33:255/418 of Q9Y823
- R43 (= R19) binding ; mutation R->A,K,Q: Abolishes the catalytic activity.
- E44 (≠ D20) binding ; binding ; binding
- Q47 (= Q23) mutation to A: Abolishes the catalytic activity.
- E74 (= E49) 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 (≠ A82) binding ; mutation to A: Substantially impairs catalytic efficiency.
- D123 (≠ A102) binding ; mutation to N: Does not affect the catalytic activity but impairs L-lysine inhibition.
- R163 (= R142) binding ; mutation R->A,Q: Abolishes the catalytic activity.; mutation to K: Severely diminishes affinity for 2-oxoglutarate and substantially impairs catalytic efficiency.
- S165 (≠ G150) binding ; mutation to A: Results in a moderate decrease in catalytic efficiency.
- E167 (≠ P152) mutation E->A,Q: Abolishes the catalytic activity.
- T197 (= T182) 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 (≠ A208) mutation to Q: Does not affect the catalytic activity but impairs L-lysine inhibition.
- H224 (= H210) binding ; binding
- H226 (= H212) 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.
Query Sequence
>5210130 FitnessBrowser__PV4:5210130
MSATNSYPSKVSIFEVGARDGLQNEKAVTTADKLTLIDQLGAAGLTRIEAGSFVSPKWVP
QMADSGDIFRQLSKRPGVVYSALTPNLKGLELALDAGADEVAIFGAASQSFSQRNINCSI
EESIERFIPVMEAAQAKQIPVRGYVSCVLGCPYEGEIQVEEVARVAEILYKMGCYEISLG
DTIGVGTPLNARRMVEAVARRVPVEKLALHFHDTYGQALANILACLETGVSVIDSSVAGL
GGCPYAKGASGNLATEDLVYMLHGMGIETGIDLNALITAGNNISQALGRVSGAKVARALT
E
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