SitesBLAST
Comparing H281DRAFT_03571 FitnessBrowser__Burk376:H281DRAFT_03571 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
69% identity, 95% coverage: 11:315/321 of query aligns to 2:305/305 of 6ndsA
- binding coenzyme a: V52 (= V61), S53 (= S62), I57 (= I66), N84 (= N93), G87 (= G96), R90 (= R99), N113 (= N122), M114 (= M123), R115 (= R124)
- binding zinc ion: D17 (= D26), H207 (= H217), H209 (= H219)
3mp3B Crystal structure of human lyase in complex with inhibitor hg-coa (see paper)
40% identity, 91% coverage: 15:305/321 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 (= R25), D15 (= D26), Q18 (= Q29), F49 (= F60), V50 (= V61), S51 (= S62), W54 (≠ A65), P81 (= P92), N82 (= N93), K84 (= K95), G85 (= G96), N111 (= N122), R122 (≠ A133), Y140 (≠ S151), S142 (≠ A153), T178 (= T189), H206 (= H217)
- binding magnesium ion: D15 (= D26), H206 (= H217), H208 (= H219)
2cw6A Crystal structure of human hmg-coa lyase: insights into catalysis and the molecular basis for hydroxymethylglutaric aciduria (see paper)
40% identity, 91% coverage: 15:305/321 of query aligns to 4:294/296 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)
40% identity, 91% coverage: 15:305/321 of query aligns to 31:321/325 of P35914
- E37 (= E21) to K: in HMGCLD; activity lower than 5% respect to the wild-type; mutation to D: Normal activity.
- R41 (= R25) to Q: in HMGCLD; loss of activity and of proton exchange; dbSNP:rs121964997; mutation to M: Reduced activity, and loss of proton exchange.
- D42 (= D26) 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 (≠ P32) to N: in HMGCLD; abolishes almost all enzymatic activity
- E72 (= E56) mutation to A: Loss of activity, and reduced affinity for metal cofactor and substrate.
- S142 (= S126) to F: in HMGCLD; activity lower than 5% respect to the wild-type
- C174 (= C158) to Y: in HMGCLD; activity lower than 5% respect to the wild-type; dbSNP:rs765475941
- F192 (≠ Y176) to S: in HMGCLD; activity lower than 5% respect to the wild-type
- I200 (= I184) to F: in HMGCLD; activity lower than 5% respect to the wild-type
- G203 (≠ A187) to E: in HMGCLD; complete loss of activity; dbSNP:rs1553131940
- D204 (= D188) mutation to A: Reduced activity, and reduced affinity for metal cofactor and substrate.
- H233 (= H217) to R: in HMGCLD; loss of activity; dbSNP:rs727503963; mutation to A: Loss of activity, and reduced proton exchange rate.
- E279 (= E263) mutation to A: Reduced thermal stability, but normal activity.
- D280 (= D264) 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)
40% identity, 89% coverage: 19:305/321 of query aligns to 8:294/296 of 3mp5B
- binding 3-hydroxy-3-methylglutaryl-coenzyme a: D15 (= D26), Q18 (= Q29), S51 (= S62), W54 (≠ A65), F100 (≠ V111), N111 (= N122), N113 (≠ R124), Y140 (≠ S151), S142 (≠ A153), T178 (= T189), C239 (= C250)
- binding magnesium ion: D15 (= D26), H206 (= H217), H208 (= H219)
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, 91% coverage: 19:309/321 of query aligns to 80:370/370 of Q8TB92
- R86 (= R25) mutation to Q: Abolishes catalytic activity.
- L237 (≠ Y176) mutation to S: Abolishes catalytic activity.
- H278 (= H217) 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)
41% identity, 84% coverage: 14:283/321 of query aligns to 1:270/283 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)
39% identity, 83% coverage: 19:283/321 of query aligns to 6:270/301 of P13703
- C237 (= C250) 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: 25:248/321 of query aligns to 30:247/399 of 6ktqA
- binding 2-oxoglutaric acid: R30 (= R25), R154 (≠ N149), T156 (≠ S151), E158 (≠ A153), S184 (≠ T185), T188 (= T189), H216 (= H217), H218 (= H219)
- binding coenzyme a: V67 (≠ A65), R96 (≠ K95), A97 (≠ G96), F116 (≠ V111), H128 (≠ M123), E158 (≠ A153)
- binding zinc ion: E31 (≠ D26), H216 (= H217), H218 (= H219)
3ivtB Homocitrate synthase lys4 bound to 2-og (see paper)
26% identity, 71% coverage: 21:248/321 of query aligns to 34:250/400 of 3ivtB
Q9Y823 Homocitrate synthase, mitochondrial; HCS; EC 2.3.3.14 from Schizosaccharomyces pombe (strain 972 / ATCC 24843) (Fission yeast) (see 2 papers)
26% identity, 71% coverage: 21:248/321 of query aligns to 39:255/418 of Q9Y823
- R43 (= R25) binding ; mutation R->A,K,Q: Abolishes the catalytic activity.
- E44 (≠ D26) binding ; binding ; binding
- Q47 (= Q29) mutation to A: Abolishes the catalytic activity.
- E74 (= E56) 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 (≠ Y87) binding ; mutation to A: Substantially impairs catalytic efficiency.
- D123 (≠ N109) binding ; mutation to N: Does not affect the catalytic activity but impairs L-lysine inhibition.
- R163 (≠ N149) binding ; mutation R->A,Q: Abolishes the catalytic activity.; mutation to K: Severely diminishes affinity for 2-oxoglutarate and substantially impairs catalytic efficiency.
- S165 (= S151) binding ; mutation to A: Results in a moderate decrease in catalytic efficiency.
- E167 (≠ A153) mutation E->A,Q: Abolishes the catalytic activity.
- T197 (= T189) 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 (≠ T215) mutation to Q: Does not affect the catalytic activity but impairs L-lysine inhibition.
- H224 (= H217) binding ; binding
- H226 (= H219) 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.
3mi3A Homocitrate synthase lys4 bound to lysine (see paper)
26% identity, 71% coverage: 21:248/321 of query aligns to 16:221/370 of 3mi3A
3ivsA Homocitrate synthase lys4 (see paper)
26% identity, 71% coverage: 21:248/321 of query aligns to 16:219/364 of 3ivsA
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)
27% identity, 65% coverage: 103:312/321 of query aligns to 180:387/503 of Q9FN52
- G263 (= G191) mutation to E: In gsm2-1; loss of activity and lack of C6, C7 and C8 aliphatic glucosinolates.
Q9FG67 Methylthioalkylmalate synthase 1, chloroplastic; 2-isopropylmalate synthase 3; EC 2.3.3.17 from Arabidopsis thaliana (Mouse-ear cress) (see paper)
27% identity, 65% coverage: 103:312/321 of query aligns to 180:387/506 of Q9FG67
- A290 (≠ T215) 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.
6e1jA Crystal structure of methylthioalkylmalate synthase (bjumam1.1) from brassica juncea (see paper)
26% identity, 69% coverage: 93:312/321 of query aligns to 102:320/409 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
3rmjB Crystal structure of truncated alpha-isopropylmalate synthase from neisseria meningitidis (see paper)
24% identity, 93% coverage: 15:312/321 of query aligns to 2:294/308 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)
25% identity, 93% coverage: 15:312/321 of query aligns to 5:297/517 of Q9JZG1
- D16 (= D26) binding
- H204 (= H217) binding
- H206 (= H219) binding
- N240 (= N259) 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)
32% identity, 39% coverage: 170:293/321 of query aligns to 160:276/453 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)
26% identity, 70% coverage: 25:248/321 of query aligns to 12:226/376 of O87198
- R12 (= R25) binding
- E13 (≠ D26) binding
- H72 (≠ A89) 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 (≠ N109) binding
- R133 (≠ A155) binding
- S135 (≠ G157) binding
- T166 (= T189) binding ; binding
- H195 (= H217) binding
- H197 (= H219) binding
Query Sequence
>H281DRAFT_03571 FitnessBrowser__Burk376:H281DRAFT_03571
MSRASNGVMDTKTADKLIVQEVAPRDGLQIEPTWVDTADKIALINALSTAGFTRIEAGSF
VSPKAIPALRDGEAVFQQIERHAGVIYVALVPNLKGAERALAAKADELNLVMSASQTHNR
ANMRMSCESSLTAFGDIVRHVKDSGVLLNASVATAFGCPFEGTIDEDRVVGIVDTYREMG
IQGITLADTTGMANPRQVTRLVTRVLERVTPSALTLHFHNTRGLGLANVLAAYEAGARRF
DAALGGLGGCPFAPGASGNICTEDLVNLCDGMGIPTGIDLEKLLALSRALPDLLGHDVPG
QVAKAGRNSDLHPVPDYVLQI
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