SitesBLAST
Comparing BPHYT_RS34520 FitnessBrowser__BFirm:BPHYT_RS34520 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)
6ndsA Structure of an hmg-coa lyase from acenitobacter baumannii in complex with coenzyme a and 3-methylmalate
71% identity, 95% coverage: 11:311/318 of query aligns to 6:305/305 of 6ndsA
- binding coenzyme a: V52 (= V57), S53 (= S58), I57 (= I62), N84 (= N89), G87 (= G92), R90 (= R95), N113 (= N118), M114 (= M119), R115 (= R120)
- binding zinc ion: D17 (= D22), H207 (= H213), H209 (= H215)
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)
39% identity, 96% coverage: 3:307/318 of query aligns to 19:325/325 of P35914
- E37 (= E17) to K: in HMGCLD; activity lower than 5% respect to the wild-type; mutation to D: Normal activity.
- R41 (= R21) to Q: in HMGCLD; loss of activity and of proton exchange; dbSNP:rs121964997; mutation to M: Reduced activity, and loss of proton exchange.
- D42 (= D22) 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 (≠ P28) to N: in HMGCLD; abolishes almost all enzymatic activity
- E72 (= E52) mutation to A: Loss of activity, and reduced affinity for metal cofactor and substrate.
- S142 (= S122) to F: in HMGCLD; activity lower than 5% respect to the wild-type
- C174 (= C154) to Y: in HMGCLD; activity lower than 5% respect to the wild-type; dbSNP:rs765475941
- F192 (≠ Y172) to S: in HMGCLD; activity lower than 5% respect to the wild-type
- I200 (= I180) to F: in HMGCLD; activity lower than 5% respect to the wild-type
- G203 (≠ A183) to E: in HMGCLD; complete loss of activity; dbSNP:rs1553131940
- D204 (= D184) mutation to A: Reduced activity, and reduced affinity for metal cofactor and substrate.
- H233 (= H213) to R: in HMGCLD; loss of activity; dbSNP:rs727503963; mutation to A: Loss of activity, and reduced proton exchange rate.
- E279 (= E259) mutation to A: Reduced thermal stability, but normal activity.
- D280 (= D260) mutation to A: Normal activity.
- C323 (= C305) 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)
40% identity, 90% coverage: 15:301/318 of query aligns to 8:294/296 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 (= R21), D15 (= D22), Q18 (= Q25), F49 (= F56), V50 (= V57), S51 (= S58), W54 (≠ A61), P81 (= P88), N82 (= N89), K84 (= K91), G85 (= G92), N111 (= N118), R122 (≠ A129), Y140 (≠ S147), S142 (≠ A149), T178 (= T185), H206 (= H213)
- binding magnesium ion: D15 (= D22), H206 (= H213), H208 (= H215)
2cw6A Crystal structure of human hmg-coa lyase: insights into catalysis and the molecular basis for hydroxymethylglutaric aciduria (see paper)
40% identity, 90% coverage: 15:301/318 of query aligns to 8:294/296 of 2cw6A
3mp5B Crystal structure of human lyase r41m in complex with hmg-coa (see paper)
40% identity, 90% coverage: 15:301/318 of query aligns to 8:294/296 of 3mp5B
- binding 3-hydroxy-3-methylglutaryl-coenzyme a: D15 (= D22), Q18 (= Q25), S51 (= S58), W54 (≠ A61), F100 (≠ V107), N111 (= N118), N113 (≠ R120), Y140 (≠ S147), S142 (≠ A149), T178 (= T185), C239 (= C246)
- binding magnesium ion: D15 (= D22), H206 (= H213), H208 (= H215)
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)
37% identity, 93% coverage: 9:304/318 of query aligns to 76:369/370 of Q8TB92
- R86 (= R21) mutation to Q: Abolishes catalytic activity.
- L237 (≠ Y172) mutation to S: Abolishes catalytic activity.
- H278 (= H213) 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.
1ydnA Crystal structure of the hmg-coa lyase from brucella melitensis, northeast structural genomics target lr35. (see paper)
42% identity, 83% coverage: 15:279/318 of query aligns to 6:270/283 of 1ydnA
P13703 Hydroxymethylglutaryl-CoA lyase; HL; HMG-CoA lyase; 3-hydroxy-3-methylglutarate-CoA lyase; EC 4.1.3.4 from Pseudomonas mevalonii (see paper)
38% identity, 87% coverage: 15:291/318 of query aligns to 6:282/301 of P13703
- C237 (= C246) 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)
26% identity, 70% coverage: 21:244/318 of query aligns to 30:247/399 of 6ktqA
- binding 2-oxoglutaric acid: R30 (= R21), R154 (≠ N145), T156 (≠ G153), E158 (≠ P155), S184 (≠ T181), T188 (= T185), H216 (= H213), H218 (= H215)
- binding coenzyme a: V67 (≠ A61), R96 (≠ K91), A97 (≠ G92), F116 (≠ V107), H128 (≠ M119), E158 (≠ P155)
- binding zinc ion: E31 (≠ D22), H216 (= H213), H218 (= H215)
3ivtB Homocitrate synthase lys4 bound to 2-og (see paper)
25% identity, 75% coverage: 8:244/318 of query aligns to 25:250/400 of 3ivtB
Q9Y823 Homocitrate synthase, mitochondrial; HCS; EC 2.3.3.14 from Schizosaccharomyces pombe (strain 972 / ATCC 24843) (Fission yeast) (see 2 papers)
25% identity, 75% coverage: 8:244/318 of query aligns to 30:255/418 of Q9Y823
- R43 (= R21) binding ; mutation R->A,K,Q: Abolishes the catalytic activity.
- E44 (≠ D22) binding ; binding ; binding
- Q47 (= Q25) mutation to A: Abolishes the catalytic activity.
- E74 (= E52) 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 (≠ Y83) binding ; mutation to A: Substantially impairs catalytic efficiency.
- D123 (≠ N105) binding ; mutation to N: Does not affect the catalytic activity but impairs L-lysine inhibition.
- R163 (≠ N145) binding ; mutation R->A,Q: Abolishes the catalytic activity.; mutation to K: Severely diminishes affinity for 2-oxoglutarate and substantially impairs catalytic efficiency.
- S165 (= S147) binding ; mutation to A: Results in a moderate decrease in catalytic efficiency.
- E167 (≠ A149) mutation E->A,Q: Abolishes the catalytic activity.
- T197 (= T185) 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 (≠ T211) mutation to Q: Does not affect the catalytic activity but impairs L-lysine inhibition.
- H224 (= H213) binding ; binding
- H226 (= H215) 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.
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)
26% identity, 64% coverage: 106:308/318 of query aligns to 187:387/503 of Q9FN52
- G263 (= G187) mutation to E: In gsm2-1; loss of activity and lack of C6, C7 and C8 aliphatic glucosinolates.
3mi3A Homocitrate synthase lys4 bound to lysine (see paper)
25% identity, 75% coverage: 8:244/318 of query aligns to 7:221/370 of 3mi3A
Q9FG67 Methylthioalkylmalate synthase 1, chloroplastic; 2-isopropylmalate synthase 3; EC 2.3.3.17 from Arabidopsis thaliana (Mouse-ear cress) (see paper)
27% identity, 63% coverage: 109:308/318 of query aligns to 190:387/506 of Q9FG67
- A290 (≠ T211) mutation to T: In gsm1-2; loss of conversion of C3 to C4 glucosinolates.
Sites not aligning to the query:
- 102 S→F: In gsm1-1; loss of conversion of C3 to C4 glucosinolates.
3ivsA Homocitrate synthase lys4 (see paper)
25% identity, 75% coverage: 8:244/318 of query aligns to 7:219/364 of 3ivsA
3rmjB Crystal structure of truncated alpha-isopropylmalate synthase from neisseria meningitidis (see paper)
23% identity, 95% coverage: 11:312/318 of query aligns to 2:298/308 of 3rmjB
6e1jA Crystal structure of methylthioalkylmalate synthase (bjumam1.1) from brassica juncea (see paper)
25% identity, 64% coverage: 106:308/318 of query aligns to 120:320/409 of 6e1jA
Sites not aligning to the query:
- binding coenzyme a: 30, 60, 63, 95, 97, 322, 323, 324, 327, 331, 359, 362, 363
- binding manganese (ii) ion: 27, 82, 84
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)
23% identity, 95% coverage: 8:308/318 of query aligns to 2:297/517 of Q9JZG1
- D16 (= D22) binding
- H204 (= H213) binding
- H206 (= H215) binding
- N240 (= N255) binding
Sites not aligning to the query:
- 366:517 Required for the condensation reaction. Not required to bind substrate
2nx9B Crystal structure of the carboxyltransferase domain of the oxaloacetate decarboxylase na+ pump from vibrio cholerae (see paper)
35% identity, 33% coverage: 174:279/318 of query aligns to 168:266/453 of 2nx9B
Sites not aligning to the query:
O87198 Homocitrate synthase; HCS; EC 2.3.3.14 from Thermus thermophilus (strain ATCC BAA-163 / DSM 7039 / HB27) (see paper)
25% identity, 70% coverage: 21:244/318 of query aligns to 12:226/376 of O87198
- R12 (= R21) binding
- E13 (≠ D22) binding
- H72 (≠ A85) 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 (≠ N105) binding
- R133 (≠ A151) binding
- S135 (≠ G153) binding
- T166 (= T185) binding ; binding
- H195 (= H213) binding
- H197 (= H215) binding
Query Sequence
>BPHYT_RS34520 FitnessBrowser__BFirm:BPHYT_RS34520
MNRVLNTSQFDKLIVQEVAPRDGLQIEPTWVETADKIALINALSTAGFTRIEGGSFVSPK
AIPALRDGEAVFQQIERQPGVIYVALIPNLKGAERALASRADELNLVMSASQTHNRANMR
MSCESSLVAFGDIVRHVKGSGVLLNGSIATAFGCPFEGKIDEDRVIGIVDTYREMGIEGI
TLADTTGMANPRQVTRLVTRVLERLPAAALTLHFHNTRGLGLANVLAAYEAGARRFDAAL
GGLGGCPFAPGASGNICTEDLVNMCDEMGIPTGIDLEKLIALSRGLPALLGHDVPGQLAK
AGRNCDLHPVPEYVLQIR
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