SitesBLAST
Comparing 201055 FitnessBrowser__MR1:201055 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)
59% identity, 96% coverage: 6:308/315 of query aligns to 18:321/325 of P35914
- E37 (= E25) to K: in HMGCLD; activity lower than 5% respect to the wild-type; mutation to D: Normal activity.
- R41 (= R29) to Q: in HMGCLD; loss of activity and of proton exchange; dbSNP:rs121964997; mutation to M: Reduced activity, and loss of proton exchange.
- D42 (= D30) 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 (≠ A36) to N: in HMGCLD; abolishes almost all enzymatic activity
- E72 (= E59) mutation to A: Loss of activity, and reduced affinity for metal cofactor and substrate.
- S142 (= S129) to F: in HMGCLD; activity lower than 5% respect to the wild-type
- C174 (= C161) to Y: in HMGCLD; activity lower than 5% respect to the wild-type; dbSNP:rs765475941
- F192 (≠ L179) to S: in HMGCLD; activity lower than 5% respect to the wild-type
- I200 (= I187) to F: in HMGCLD; activity lower than 5% respect to the wild-type
- G203 (= G190) to E: in HMGCLD; complete loss of activity; dbSNP:rs1553131940
- D204 (= D191) mutation to A: Reduced activity, and reduced affinity for metal cofactor and substrate.
- H233 (= H220) to R: in HMGCLD; loss of activity; dbSNP:rs727503963; mutation to A: Loss of activity, and reduced proton exchange rate.
- E279 (= E266) mutation to A: Reduced thermal stability, but normal activity.
- D280 (= D267) 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)
61% identity, 91% coverage: 21:308/315 of query aligns to 6:294/296 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 (= R29), D15 (= D30), Q18 (= Q33), F49 (= F63), V50 (= V64), S51 (= S65), W54 (= W68), P81 (= P95), N82 (= N96), K84 (= K98), G85 (= G99), N111 (= N125), R122 (= R136), Y140 (= Y154), S142 (= S156), T178 (= T192), H206 (= H220)
- binding magnesium ion: D15 (= D30), H206 (= H220), H208 (= H222)
2cw6A Crystal structure of human hmg-coa lyase: insights into catalysis and the molecular basis for hydroxymethylglutaric aciduria (see paper)
61% identity, 91% coverage: 21:308/315 of query aligns to 6:294/296 of 2cw6A
3mp5B Crystal structure of human lyase r41m in complex with hmg-coa (see paper)
61% identity, 91% coverage: 21:308/315 of query aligns to 6:294/296 of 3mp5B
- binding 3-hydroxy-3-methylglutaryl-coenzyme a: D15 (= D30), Q18 (= Q33), S51 (= S65), W54 (= W68), F100 (= F114), N111 (= N125), N113 (= N127), Y140 (= Y154), S142 (= S156), T178 (= T192), C239 (= C253)
- binding magnesium ion: D15 (= D30), H206 (= H220), H208 (= H222)
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)
56% identity, 96% coverage: 8:308/315 of query aligns to 65:366/370 of Q8TB92
- R86 (= R29) mutation to Q: Abolishes catalytic activity.
- L237 (= L179) mutation to S: Abolishes catalytic activity.
- H278 (= H220) 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, 92% coverage: 20:309/315 of query aligns to 3:293/301 of P13703
- C237 (= C253) active site
1ydnA Crystal structure of the hmg-coa lyase from brucella melitensis, northeast structural genomics target lr35. (see paper)
54% identity, 87% coverage: 18:291/315 of query aligns to 1:275/283 of 1ydnA
6ndsA Structure of an hmg-coa lyase from acenitobacter baumannii in complex with coenzyme a and 3-methylmalate
41% identity, 87% coverage: 14:286/315 of query aligns to 1:273/305 of 6ndsA
- binding coenzyme a: V52 (= V64), S53 (= S65), I57 (≠ V69), N84 (= N96), G87 (= G99), R90 (≠ L102), N113 (= N125), M114 (≠ I126), R115 (≠ N127)
- binding zinc ion: D17 (= D30), H207 (= H220), H209 (= H222)
6ktqA Crystal structure of catalytic domain of homocitrate synthase from sulfolobus acidocaldarius (sahcs(dram)) in complex with alpha- ketoglutarate/zn2+/coa (see paper)
23% identity, 73% coverage: 21:251/315 of query aligns to 22:247/399 of 6ktqA
- binding 2-oxoglutaric acid: R30 (= R29), R154 (= R152), T156 (≠ Y154), E158 (≠ S156), S184 (= S188), T188 (= T192), H216 (= H220), H218 (= H222)
- binding coenzyme a: V67 (≠ W68), R96 (≠ K98), A97 (≠ G99), F116 (= F114), H128 (≠ I126), E158 (≠ S156)
- binding zinc ion: E31 (≠ D30), H216 (= H220), H218 (= H222)
2nx9B Crystal structure of the carboxyltransferase domain of the oxaloacetate decarboxylase na+ pump from vibrio cholerae (see paper)
33% identity, 36% coverage: 175:286/315 of query aligns to 162:266/453 of 2nx9B
Sites not aligning to the query:
3rmjB Crystal structure of truncated alpha-isopropylmalate synthase from neisseria meningitidis (see paper)
25% identity, 95% coverage: 18:315/315 of query aligns to 1:291/308 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, 85% coverage: 18:286/315 of query aligns to 4:268/517 of Q9JZG1
- D16 (= D30) binding
- H204 (= H220) binding
- H206 (= H222) binding
- N240 (= N262) binding
Sites not aligning to the query:
- 366:517 Required for the condensation reaction. Not required to bind substrate
Q9Y823 Homocitrate synthase, mitochondrial; HCS; EC 2.3.3.14 from Schizosaccharomyces pombe (strain 972 / ATCC 24843) (Fission yeast) (see 2 papers)
23% identity, 85% coverage: 19:286/315 of query aligns to 33:293/418 of Q9Y823
- R43 (= R29) binding ; mutation R->A,K,Q: Abolishes the catalytic activity.
- E44 (≠ D30) binding ; binding ; binding
- Q47 (= Q33) mutation to A: Abolishes the catalytic activity.
- E74 (= E59) 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 (≠ Q81) binding ; mutation to A: Substantially impairs catalytic efficiency.
- D123 (≠ E101) binding ; mutation to N: Does not affect the catalytic activity but impairs L-lysine inhibition.
- R163 (= R152) binding ; mutation R->A,Q: Abolishes the catalytic activity.; mutation to K: Severely diminishes affinity for 2-oxoglutarate and substantially impairs catalytic efficiency.
- S165 (≠ P162) binding ; mutation to A: Results in a moderate decrease in catalytic efficiency.
- E167 (= E164) mutation E->A,Q: Abolishes the catalytic activity.
- T197 (= T192) 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 (≠ A218) mutation to Q: Does not affect the catalytic activity but impairs L-lysine inhibition.
- H224 (= H220) binding ; binding
- H226 (= H222) binding ; binding
- R288 (≠ I281) 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.
3ivtB Homocitrate synthase lys4 bound to 2-og (see paper)
23% identity, 85% coverage: 19:286/315 of query aligns to 28:288/400 of 3ivtB
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)
24% identity, 54% coverage: 106:276/315 of query aligns to 180:342/503 of Q9FN52
- G263 (= G194) 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)
23% identity, 85% coverage: 19:286/315 of query aligns to 10:259/370 of 3mi3A
O87198 Homocitrate synthase; HCS; EC 2.3.3.14 from Thermus thermophilus (strain ATCC BAA-163 / DSM 7039 / HB27) (see paper)
26% identity, 71% coverage: 29:251/315 of query aligns to 12:226/376 of O87198
- R12 (= R29) binding
- E13 (≠ D30) binding
- H72 (≠ S91) 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 (≠ E101) binding
- R133 (= R152) binding
- S135 (≠ Y154) binding
- T166 (= T192) binding ; binding
- H195 (= H220) binding
- H197 (= H222) binding
6e1jA Crystal structure of methylthioalkylmalate synthase (bjumam1.1) from brassica juncea (see paper)
23% identity, 81% coverage: 21:276/315 of query aligns to 18:275/409 of 6e1jA
- binding coenzyme a: Q30 (= Q33), F60 (≠ S62), S63 (= S65), I95 (≠ V89), R97 (≠ S91), F121 (= F114), K132 (≠ N125), L133 (≠ I126)
- binding 4-(methylsulfanyl)-2-oxobutanoic acid: P192 (≠ G190), T194 (= T192), H225 (= H220), H227 (= H222)
- binding manganese (ii) ion: D27 (= D30), V82 (vs. gap), E84 (vs. gap), H225 (= H220), H227 (= H222)
Sites not aligning to the query:
2zyfA Crystal structure of homocitrate synthase from thermus thermophilus complexed with magnesuim ion and alpha-ketoglutarate (see paper)
26% identity, 71% coverage: 29:251/315 of query aligns to 12:220/314 of 2zyfA
2ztjA Crystal structure of homocitrate synthase from thermus thermophilus complexed with alpha-ketoglutarate (see paper)
27% identity, 71% coverage: 29:251/315 of query aligns to 12:218/312 of 2ztjA
Query Sequence
>201055 FitnessBrowser__MR1:201055
MSAQDLSNLSATSLSATSDSVSLFEMGPRDGLQNEAAVPTQAKVALIEALANAGVKRIEA
GSFVSPKWVPQMADSGEVLRQIRRQAGVVYSALTPNVKGLELALDAKASEVAIFGAASQS
FSQRNINCSIEESIERFIPLMDMAKAANIPVRGYVSCVLGCPYEGEIAASEVARVSEILY
KMGCYEISLGDTIGVGTPLKARKMLQAVMERVPVEKLALHFHDTYGQALANITACLDLGV
RSFDASVAGLGGCPYAKGASGNLASEDLVYMLHGLGLKTGIDLEKLALAGFGISKQLNRL
NGSKVANAILQGAKA
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