SitesBLAST
Comparing Ac3H11_370 FitnessBrowser__acidovorax_3H11:Ac3H11_370 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)
6ndsA Structure of an hmg-coa lyase from acenitobacter baumannii in complex with coenzyme a and 3-methylmalate
52% identity, 91% coverage: 17:313/326 of query aligns to 10:305/305 of 6ndsA
- binding coenzyme a: V52 (≠ T59), S53 (= S60), I57 (= I64), N84 (= N91), G87 (= G94), R90 (= R97), N113 (= N120), M114 (≠ L121), R115 (= R122)
- binding zinc ion: D17 (= D24), H207 (= H215), H209 (= H217)
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)
38% identity, 90% coverage: 13:307/326 of query aligns to 31:325/325 of P35914
- E37 (= E19) to K: in HMGCLD; activity lower than 5% respect to the wild-type; mutation to D: Normal activity.
- R41 (= R23) to Q: in HMGCLD; loss of activity and of proton exchange; dbSNP:rs121964997; mutation to M: Reduced activity, and loss of proton exchange.
- D42 (= D24) 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 (= K30) to N: in HMGCLD; abolishes almost all enzymatic activity
- E72 (= E54) mutation to A: Loss of activity, and reduced affinity for metal cofactor and substrate.
- S142 (≠ T124) to F: in HMGCLD; activity lower than 5% respect to the wild-type
- C174 (= C156) to Y: in HMGCLD; activity lower than 5% respect to the wild-type; dbSNP:rs765475941
- F192 (= F174) to S: in HMGCLD; activity lower than 5% respect to the wild-type
- I200 (= I182) to F: in HMGCLD; activity lower than 5% respect to the wild-type
- G203 (≠ C185) to E: in HMGCLD; complete loss of activity; dbSNP:rs1553131940
- D204 (= D186) mutation to A: Reduced activity, and reduced affinity for metal cofactor and substrate.
- H233 (= H215) to R: in HMGCLD; loss of activity; dbSNP:rs727503963; mutation to A: Loss of activity, and reduced proton exchange rate.
- E279 (= E261) mutation to A: Reduced thermal stability, but normal activity.
- D280 (≠ E262) mutation to A: Normal activity.
- C323 (≠ P305) modified: Interchain; mutation to S: Abolishes interchain homodimerization. Exhibits no DTT stimulated activity.
3mp3B Crystal structure of human lyase in complex with inhibitor hg-coa (see paper)
38% identity, 89% coverage: 13:303/326 of query aligns to 4:294/296 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 (= R23), D15 (= D24), Q18 (= Q27), F49 (= F58), V50 (≠ T59), S51 (= S60), W54 (≠ A63), P81 (= P90), N82 (= N91), K84 (≠ R93), G85 (= G94), N111 (= N120), R122 (≠ A131), Y140 (≠ S149), S142 (= S151), T178 (= T187), H206 (= H215)
- binding magnesium ion: D15 (= D24), H206 (= H215), H208 (= H217)
2cw6A Crystal structure of human hmg-coa lyase: insights into catalysis and the molecular basis for hydroxymethylglutaric aciduria (see paper)
38% identity, 89% coverage: 13:303/326 of query aligns to 4:294/296 of 2cw6A
3mp5B Crystal structure of human lyase r41m in complex with hmg-coa (see paper)
38% identity, 89% coverage: 13:303/326 of query aligns to 4:294/296 of 3mp5B
- binding 3-hydroxy-3-methylglutaryl-coenzyme a: D15 (= D24), Q18 (= Q27), S51 (= S60), W54 (≠ A63), F100 (≠ V109), N111 (= N120), N113 (≠ R122), Y140 (≠ S149), S142 (= S151), T178 (= T187), C239 (= C248)
- binding magnesium ion: D15 (= D24), H206 (= H215), H208 (= H217)
1ydnA Crystal structure of the hmg-coa lyase from brucella melitensis, northeast structural genomics target lr35. (see paper)
41% identity, 83% coverage: 15:284/326 of query aligns to 4:273/283 of 1ydnA
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)
36% identity, 89% coverage: 15:303/326 of query aligns to 78:366/370 of Q8TB92
- R86 (= R23) mutation to Q: Abolishes catalytic activity.
- L237 (≠ F174) mutation to S: Abolishes catalytic activity.
- H278 (= H215) 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)
37% identity, 86% coverage: 15:293/326 of query aligns to 4:282/301 of P13703
- C237 (= C248) active site
6ktqA Crystal structure of catalytic domain of homocitrate synthase from sulfolobus acidocaldarius (sahcs(dram)) in complex with alpha- ketoglutarate/zn2+/coa (see paper)
27% identity, 71% coverage: 15:246/326 of query aligns to 18:247/399 of 6ktqA
- binding 2-oxoglutaric acid: R30 (= R23), R154 (≠ N147), T156 (≠ S149), E158 (≠ S151), S184 (≠ T183), T188 (= T187), H216 (= H215), H218 (= H217)
- binding coenzyme a: V67 (≠ A63), R96 (= R93), A97 (≠ G94), F116 (≠ V109), H128 (≠ L121), E158 (≠ S151)
- binding zinc ion: E31 (≠ D24), H216 (= H215), H218 (= H217)
2zyfA Crystal structure of homocitrate synthase from thermus thermophilus complexed with magnesuim ion and alpha-ketoglutarate (see paper)
32% identity, 69% coverage: 22:246/326 of query aligns to 11:220/314 of 2zyfA
3rmjB Crystal structure of truncated alpha-isopropylmalate synthase from neisseria meningitidis (see paper)
27% identity, 89% coverage: 14:303/326 of query aligns to 3:285/308 of 3rmjB
O87198 Homocitrate synthase; HCS; EC 2.3.3.14 from Thermus thermophilus (strain ATCC BAA-163 / DSM 7039 / HB27) (see paper)
32% identity, 69% coverage: 22:246/326 of query aligns to 11:226/376 of O87198
- R12 (= R23) binding
- E13 (≠ D24) binding
- H72 (≠ A87) 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 (≠ N107) binding
- R133 (≠ N147) binding
- S135 (= S149) binding
- T166 (= T187) binding ; binding
- H195 (= H215) binding
- H197 (= H217) binding
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)
27% identity, 89% coverage: 14:303/326 of query aligns to 6:288/517 of Q9JZG1
- D16 (= D24) binding
- H204 (= H215) binding
- H206 (= H217) binding
- N240 (= N257) binding
Sites not aligning to the query:
- 366:517 Required for the condensation reaction. Not required to bind substrate
3a9iA Crystal structure of homocitrate synthase from thermus thermophilus complexed with lys (see paper)
32% identity, 69% coverage: 22:246/326 of query aligns to 10:219/347 of 3a9iA
3mi3A Homocitrate synthase lys4 bound to lysine (see paper)
27% identity, 70% coverage: 19:246/326 of query aligns to 16:221/370 of 3mi3A
3ivtB Homocitrate synthase lys4 bound to 2-og (see paper)
26% identity, 70% coverage: 19:246/326 of query aligns to 34:250/400 of 3ivtB
2ztjA Crystal structure of homocitrate synthase from thermus thermophilus complexed with alpha-ketoglutarate (see paper)
31% identity, 69% coverage: 22:246/326 of query aligns to 11:218/312 of 2ztjA
Q9Y823 Homocitrate synthase, mitochondrial; HCS; EC 2.3.3.14 from Schizosaccharomyces pombe (strain 972 / ATCC 24843) (Fission yeast) (see 2 papers)
26% identity, 70% coverage: 19:246/326 of query aligns to 39:255/418 of Q9Y823
- R43 (= R23) binding ; mutation R->A,K,Q: Abolishes the catalytic activity.
- E44 (≠ D24) binding ; binding ; binding
- Q47 (= Q27) mutation to A: Abolishes the catalytic activity.
- E74 (= E54) 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 (≠ A87) binding ; mutation to A: Substantially impairs catalytic efficiency.
- D123 (≠ N107) binding ; mutation to N: Does not affect the catalytic activity but impairs L-lysine inhibition.
- R163 (≠ N147) binding ; mutation R->A,Q: Abolishes the catalytic activity.; mutation to K: Severely diminishes affinity for 2-oxoglutarate and substantially impairs catalytic efficiency.
- S165 (= S149) binding ; mutation to A: Results in a moderate decrease in catalytic efficiency.
- E167 (≠ S151) mutation E->A,Q: Abolishes the catalytic activity.
- T197 (= T187) 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 (≠ T213) mutation to Q: Does not affect the catalytic activity but impairs L-lysine inhibition.
- H224 (= H215) binding ; binding
- H226 (= H217) 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.
3ivsA Homocitrate synthase lys4 (see paper)
26% identity, 70% coverage: 19:246/326 of query aligns to 16:219/364 of 3ivsA
6e1jA Crystal structure of methylthioalkylmalate synthase (bjumam1.1) from brassica juncea (see paper)
24% identity, 83% coverage: 22:293/326 of query aligns to 25:303/409 of 6e1jA
- binding coenzyme a: Q30 (= Q27), F60 (≠ T56), S63 (≠ T59), I95 (≠ P90), R97 (= R93), F121 (≠ V109), K132 (≠ N120), L133 (= L121)
- binding 4-(methylsulfanyl)-2-oxobutanoic acid: P192 (≠ C185), T194 (= T187), H225 (= H215), H227 (= H217)
- binding manganese (ii) ion: D27 (= D24), V82 (≠ I77), E84 (≠ R79), H225 (= H215), H227 (= H217)
Sites not aligning to the query:
Query Sequence
>Ac3H11_370 FitnessBrowser__acidovorax_3H11:Ac3H11_370
MSASSTVWQGANRRIHMQEVGLRDGLQMEKAFVPTADKIALCNALSAAGLSKIEVTSFTS
PTAIPALKDAEVVMREITRRPGTVYTALVPNLRGAERAIESRTDELNLVMSVSATHNLAN
LRMTQEQSFAALAQVVALAQGANVAVNVSLSCVFGCPMEGDVAQADVFGWVQRFVDVGVR
GITLCDTTGMAYPTQVHQLTAAARARWPGVEFTLHFHNTRGMGLANVLAAIDAGADRFDA
SLGGLGGCPYAPGASGNVCSEEIVHALALMGYDTGVDLVQLVAAAQQLPAFIGHDIPSQI
AKAGPRLALHPVPADFEAIRERSLSR
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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