SitesBLAST
Comparing GFF1022 FitnessBrowser__Marino:GFF1022 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)
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, 98% coverage: 3:296/301 of query aligns to 29:321/325 of P35914
- E37 (= E11) to K: in HMGCLD; activity lower than 5% respect to the wild-type; mutation to D: Normal activity.
- R41 (= R15) to Q: in HMGCLD; loss of activity and of proton exchange; dbSNP:rs121964997; mutation to M: Reduced activity, and loss of proton exchange.
- D42 (= D16) 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 (≠ P22) to N: in HMGCLD; abolishes almost all enzymatic activity
- E72 (= E47) mutation to A: Loss of activity, and reduced affinity for metal cofactor and substrate.
- S142 (≠ T117) to F: in HMGCLD; activity lower than 5% respect to the wild-type
- C174 (= C149) to Y: in HMGCLD; activity lower than 5% respect to the wild-type; dbSNP:rs765475941
- F192 (≠ L167) to S: in HMGCLD; activity lower than 5% respect to the wild-type
- I200 (= I175) to F: in HMGCLD; activity lower than 5% respect to the wild-type
- G203 (= G178) to E: in HMGCLD; complete loss of activity; dbSNP:rs1553131940
- D204 (= D179) mutation to A: Reduced activity, and reduced affinity for metal cofactor and substrate.
- H233 (= H208) to R: in HMGCLD; loss of activity; dbSNP:rs727503963; mutation to A: Loss of activity, and reduced proton exchange rate.
- E279 (= E254) mutation to A: Reduced thermal stability, but normal activity.
- D280 (= D255) 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)
62% identity, 98% coverage: 3:296/301 of query aligns to 2:294/296 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 (= R15), D15 (= D16), Q18 (= Q19), F49 (= F51), V50 (= V52), S51 (= S53), W54 (= W56), P81 (= P83), N82 (= N84), K84 (= K86), G85 (= G87), N111 (= N113), R122 (= R124), Y140 (= Y142), S142 (= S144), T178 (= T180), H206 (= H208)
- binding magnesium ion: D15 (= D16), H206 (= H208), H208 (= H210)
2cw6A Crystal structure of human hmg-coa lyase: insights into catalysis and the molecular basis for hydroxymethylglutaric aciduria (see paper)
62% identity, 98% coverage: 3:296/301 of query aligns to 2:294/296 of 2cw6A
3mp5B Crystal structure of human lyase r41m in complex with hmg-coa (see paper)
62% identity, 98% coverage: 3:296/301 of query aligns to 2:294/296 of 3mp5B
- binding 3-hydroxy-3-methylglutaryl-coenzyme a: D15 (= D16), Q18 (= Q19), S51 (= S53), W54 (= W56), F100 (= F102), N111 (= N113), N113 (= N115), Y140 (= Y142), S142 (= S144), T178 (= T180), C239 (= C241)
- binding magnesium ion: D15 (= D16), H206 (= H208), H208 (= H210)
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)
61% identity, 98% coverage: 3:296/301 of query aligns to 74:366/370 of Q8TB92
- R86 (= R15) mutation to Q: Abolishes catalytic activity.
- L237 (= L167) mutation to S: Abolishes catalytic activity.
- H278 (= H208) 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)
56% identity, 97% coverage: 5:297/301 of query aligns to 2:293/301 of P13703
- C237 (= C241) active site
1ydnA Crystal structure of the hmg-coa lyase from brucella melitensis, northeast structural genomics target lr35. (see paper)
57% identity, 91% coverage: 5:278/301 of query aligns to 2:274/283 of 1ydnA
6ndsA Structure of an hmg-coa lyase from acenitobacter baumannii in complex with coenzyme a and 3-methylmalate
39% identity, 98% coverage: 2:296/301 of query aligns to 3:295/305 of 6ndsA
- binding coenzyme a: V52 (= V52), S53 (= S53), I57 (≠ V57), N84 (= N84), G87 (= G87), R90 (≠ G90), N113 (= N113), M114 (≠ I114), R115 (≠ N115)
- binding zinc ion: D17 (= D16), H207 (= H208), H209 (= H210)
6ktqA Crystal structure of catalytic domain of homocitrate synthase from sulfolobus acidocaldarius (sahcs(dram)) in complex with alpha- ketoglutarate/zn2+/coa (see paper)
25% identity, 78% coverage: 6:239/301 of query aligns to 21:247/399 of 6ktqA
- binding 2-oxoglutaric acid: R30 (= R15), R154 (= R140), T156 (≠ Y142), E158 (≠ S144), S184 (= S176), T188 (= T180), H216 (= H208), H218 (= H210)
- binding coenzyme a: V67 (≠ W56), R96 (≠ L85), A97 (vs. gap), F116 (= F102), H128 (≠ I114), E158 (≠ S144)
- binding zinc ion: E31 (≠ D16), H216 (= H208), H218 (= H210)
2nx9B Crystal structure of the carboxyltransferase domain of the oxaloacetate decarboxylase na+ pump from vibrio cholerae (see paper)
32% identity, 37% coverage: 163:274/301 of query aligns to 162:266/453 of 2nx9B
Sites not aligning to the query:
3ivtB Homocitrate synthase lys4 bound to 2-og (see paper)
23% identity, 89% coverage: 9:276/301 of query aligns to 32:290/400 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, 89% coverage: 9:276/301 of query aligns to 37:295/418 of Q9Y823
- R43 (= R15) binding ; mutation R->A,K,Q: Abolishes the catalytic activity.
- E44 (≠ D16) binding ; binding ; binding
- Q47 (= Q19) mutation to A: Abolishes the catalytic activity.
- E74 (= E47) 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 (≠ A80) binding ; mutation to A: Substantially impairs catalytic efficiency.
- D123 (≠ A100) binding ; mutation to N: Does not affect the catalytic activity but impairs L-lysine inhibition.
- R163 (= R140) binding ; mutation R->A,Q: Abolishes the catalytic activity.; mutation to K: Severely diminishes affinity for 2-oxoglutarate and substantially impairs catalytic efficiency.
- S165 (≠ Y142) binding ; mutation to A: Results in a moderate decrease in catalytic efficiency.
- E167 (≠ S144) mutation E->A,Q: Abolishes the catalytic activity.
- T197 (= T180) 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 (≠ A206) mutation to Q: Does not affect the catalytic activity but impairs L-lysine inhibition.
- H224 (= H208) binding ; binding
- H226 (= H210) binding ; binding
- R288 (≠ V269) mutation to K: Does not affect the catalytic activity but impairs L-lysine inhibition.
Sites not aligning to the query:
- 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)
29% identity, 38% coverage: 162:276/301 of query aligns to 143:259/364 of 3ivsA
Sites not aligning to the query:
3mi3A Homocitrate synthase lys4 bound to lysine (see paper)
29% identity, 38% coverage: 162:276/301 of query aligns to 145:261/370 of 3mi3A
Sites not aligning to the query:
6e1jA Crystal structure of methylthioalkylmalate synthase (bjumam1.1) from brassica juncea (see paper)
22% identity, 91% coverage: 7:281/301 of query aligns to 18:298/409 of 6e1jA
- binding coenzyme a: Q30 (= Q19), F60 (≠ S50), S63 (= S53), I95 (≠ R77), R97 (≠ S79), F121 (= F102), K132 (≠ N113), L133 (≠ I114)
- binding 4-(methylsulfanyl)-2-oxobutanoic acid: P192 (≠ G178), T194 (= T180), H225 (= H208), H227 (= H210)
- binding manganese (ii) ion: D27 (= D16), V82 (≠ A64), E84 (≠ V66), H225 (= H208), H227 (= H210)
Sites not aligning to the query:
4jn6C Crystal structure of the aldolase-dehydrogenase complex from mycobacterium tuberculosis hrv37 (see paper)
26% identity, 54% coverage: 108:271/301 of query aligns to 103:252/339 of 4jn6C
Sites not aligning to the query:
3rmjB Crystal structure of truncated alpha-isopropylmalate synthase from neisseria meningitidis (see paper)
26% identity, 41% coverage: 160:283/301 of query aligns to 150:274/308 of 3rmjB
Sites not aligning to the query:
P9WMK5 4-hydroxy-2-oxohexanoate aldolase; 4-hydroxy-2-keto-pentanoic acid aldolase; 4-hydroxy-2-oxopentanoate aldolase; 4-hydroxy-2-oxovalerate aldolase; HOA; EC 4.1.3.43; EC 4.1.3.39 from Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv) (see paper)
26% identity, 54% coverage: 108:271/301 of query aligns to 106:255/346 of P9WMK5
- H198 (= H208) binding
- H200 (= H210) binding
Sites not aligning to the query:
- 16 binding
- 322 G→F: Abolishes substrate channeling to HsaG.
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)
26% identity, 41% coverage: 160:283/301 of query aligns to 153:277/517 of Q9JZG1
- H204 (= H208) binding
- H206 (= H210) binding
- N240 (= N250) binding
Sites not aligning to the query:
- 16 binding
- 366:517 Required for the condensation reaction. Not required to bind substrate
Q9FG67 Methylthioalkylmalate synthase 1, chloroplastic; 2-isopropylmalate synthase 3; EC 2.3.3.17 from Arabidopsis thaliana (Mouse-ear cress) (see paper)
23% identity, 64% coverage: 88:281/301 of query aligns to 174:365/506 of Q9FG67
- A290 (= A206) 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.
Query Sequence
>GFF1022 FitnessBrowser__Marino:GFF1022
MAFPKQVRLVEMSPRDGLQNEPGPVIATAIKTGLIDRLADSGLSHIEAASFVSPKWVPQM
GDAAEVMAGITRKAGVRYSALTPNLKGFEGALAAKADEVAVFGAASESFTKKNINCTIAE
SLERFAPVVEEARKHGIPVRGYVSTVMGCPYEGDIAPEQVATVAKALYDMGCHEISLGDT
IGVGTPIKAKRMLEAVAAHVPMDKLAAHFHDTYGQALANLYAVLEEGVSVIDASVAGLGG
CPYAKGASGNVATEDVLYLLNGLGIKTGVDLEKLVATGDWICSQLNRHNGSKVGQAMGGN
C
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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