SitesBLAST
Comparing Pf6N2E2_1040 FitnessBrowser__pseudo6_N2E2:Pf6N2E2_1040 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
40% identity, 86% coverage: 9:278/313 of query aligns to 8:274/305 of 6ndsA
- binding coenzyme a: V52 (= V53), S53 (= S54), I57 (≠ L58), N84 (= N85), G87 (= G88), R90 (≠ A91), N113 (= N114), M114 (≠ I115), R115 (= R116)
- binding zinc ion: D17 (= D18), H207 (= H211), H209 (= H213)
3mp3B Crystal structure of human lyase in complex with inhibitor hg-coa (see paper)
39% identity, 89% coverage: 9:288/313 of query aligns to 6:283/296 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 (= R17), D15 (= D18), Q18 (= Q21), F49 (= F52), V50 (= V53), S51 (= S54), W54 (≠ L57), P81 (= P84), N82 (= N85), K84 (= K87), G85 (= G88), N111 (= N114), R122 (≠ E125), Y140 (≠ G145), S142 (= S147), T178 (= T183), H206 (= H211)
- binding magnesium ion: D15 (= D18), H206 (= H211), H208 (= H213)
2cw6A Crystal structure of human hmg-coa lyase: insights into catalysis and the molecular basis for hydroxymethylglutaric aciduria (see paper)
39% identity, 89% coverage: 9:288/313 of query aligns to 6:283/296 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)
39% identity, 89% coverage: 9:288/313 of query aligns to 33:310/325 of P35914
- E37 (= E13) to K: in HMGCLD; activity lower than 5% respect to the wild-type; mutation to D: Normal activity.
- R41 (= R17) to Q: in HMGCLD; loss of activity and of proton exchange; dbSNP:rs121964997; mutation to M: Reduced activity, and loss of proton exchange.
- D42 (= D18) 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 (≠ S24) to N: in HMGCLD; abolishes almost all enzymatic activity
- E72 (= E48) mutation to A: Loss of activity, and reduced affinity for metal cofactor and substrate.
- S142 (≠ T118) to F: in HMGCLD; activity lower than 5% respect to the wild-type
- C174 (= C152) to Y: in HMGCLD; activity lower than 5% respect to the wild-type; dbSNP:rs765475941
- F192 (≠ M170) to S: in HMGCLD; activity lower than 5% respect to the wild-type
- I200 (≠ V178) to F: in HMGCLD; activity lower than 5% respect to the wild-type
- G203 (≠ A181) to E: in HMGCLD; complete loss of activity; dbSNP:rs1553131940
- D204 (= D182) mutation to A: Reduced activity, and reduced affinity for metal cofactor and substrate.
- H233 (= H211) to R: in HMGCLD; loss of activity; dbSNP:rs727503963; mutation to A: Loss of activity, and reduced proton exchange rate.
- E279 (= E257) mutation to A: Reduced thermal stability, but normal activity.
- D280 (= D258) 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)
38% identity, 89% coverage: 9:288/313 of query aligns to 6:283/296 of 3mp5B
- binding 3-hydroxy-3-methylglutaryl-coenzyme a: D15 (= D18), Q18 (= Q21), S51 (= S54), W54 (≠ L57), F100 (≠ P103), N111 (= N114), N113 (≠ R116), Y140 (≠ G145), S142 (= S147), T178 (= T183), C239 (= C244)
- binding magnesium ion: D15 (= D18), H206 (= H211), H208 (= H213)
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)
35% identity, 89% coverage: 9:288/313 of query aligns to 78:355/370 of Q8TB92
- R86 (= R17) mutation to Q: Abolishes catalytic activity.
- L237 (≠ M170) mutation to S: Abolishes catalytic activity.
- H278 (= H211) 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)
41% identity, 86% coverage: 9:277/313 of query aligns to 4:270/301 of P13703
- C237 (= C244) active site
1ydnA Crystal structure of the hmg-coa lyase from brucella melitensis, northeast structural genomics target lr35. (see paper)
38% identity, 86% coverage: 11:280/313 of query aligns to 6:273/283 of 1ydnA
O87198 Homocitrate synthase; HCS; EC 2.3.3.14 from Thermus thermophilus (strain ATCC BAA-163 / DSM 7039 / HB27) (see paper)
31% identity, 84% coverage: 17:279/313 of query aligns to 12:266/376 of O87198
- R12 (= R17) binding
- E13 (≠ D18) binding
- H72 (≠ A81) 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 (≠ T101) binding
- R133 (≠ E143) binding
- S135 (≠ G145) binding
- T166 (= T183) binding ; binding
- H195 (= H211) binding
- H197 (= H213) binding
2zyfA Crystal structure of homocitrate synthase from thermus thermophilus complexed with magnesuim ion and alpha-ketoglutarate (see paper)
30% identity, 84% coverage: 17:279/313 of query aligns to 12:260/314 of 2zyfA
3a9iA Crystal structure of homocitrate synthase from thermus thermophilus complexed with lys (see paper)
30% identity, 84% coverage: 17:279/313 of query aligns to 11:259/347 of 3a9iA
2ztjA Crystal structure of homocitrate synthase from thermus thermophilus complexed with alpha-ketoglutarate (see paper)
30% identity, 84% coverage: 17:279/313 of query aligns to 12:258/312 of 2ztjA
3ivtB Homocitrate synthase lys4 bound to 2-og (see paper)
28% identity, 76% coverage: 5:242/313 of query aligns to 28:250/400 of 3ivtB
Q9Y823 Homocitrate synthase, mitochondrial; HCS; EC 2.3.3.14 from Schizosaccharomyces pombe (strain 972 / ATCC 24843) (Fission yeast) (see 2 papers)
28% identity, 76% coverage: 5:242/313 of query aligns to 33:255/418 of Q9Y823
- R43 (= R17) binding ; mutation R->A,K,Q: Abolishes the catalytic activity.
- E44 (≠ D18) binding ; binding ; binding
- Q47 (= Q21) mutation to A: Abolishes the catalytic activity.
- E74 (= E48) 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 (≠ A81) binding ; mutation to A: Substantially impairs catalytic efficiency.
- D123 (≠ T101) binding ; mutation to N: Does not affect the catalytic activity but impairs L-lysine inhibition.
- R163 (≠ V149) binding ; mutation R->A,Q: Abolishes the catalytic activity.; mutation to K: Severely diminishes affinity for 2-oxoglutarate and substantially impairs catalytic efficiency.
- S165 (≠ G151) binding ; mutation to A: Results in a moderate decrease in catalytic efficiency.
- E167 (≠ T153) mutation E->A,Q: Abolishes the catalytic activity.
- T197 (= T183) 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 (≠ S209) mutation to Q: Does not affect the catalytic activity but impairs L-lysine inhibition.
- H224 (= H211) binding ; binding
- H226 (= H213) 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)
28% identity, 76% coverage: 5:242/313 of query aligns to 10:221/370 of 3mi3A
3ivsA Homocitrate synthase lys4 (see paper)
27% identity, 76% coverage: 5:242/313 of query aligns to 10:219/364 of 3ivsA
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, 94% coverage: 17:310/313 of query aligns to 30:313/399 of 6ktqA
- binding 2-oxoglutaric acid: R30 (= R17), R154 (≠ V149), T156 (≠ G151), E158 (≠ T153), S184 (≠ G179), T188 (= T183), H216 (= H211), H218 (= H213)
- binding coenzyme a: V67 (≠ L57), R96 (≠ K87), A97 (≠ G88), F116 (≠ P103), H128 (= H119), E158 (≠ T153)
- binding zinc ion: E31 (≠ D18), H216 (= H211), H218 (= H213)
3rmjB Crystal structure of truncated alpha-isopropylmalate synthase from neisseria meningitidis (see paper)
25% identity, 91% coverage: 9:292/313 of query aligns to 4:282/308 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: 1:292/313 of query aligns to 1:285/517 of Q9JZG1
- D16 (= D18) binding
- H204 (= H211) binding
- H206 (= H213) binding
- N240 (= N253) binding
Sites not aligning to the query:
- 366:517 Required for the condensation reaction. Not required to bind substrate
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)
25% identity, 97% coverage: 3:305/313 of query aligns to 81:394/503 of Q9FN52
- G263 (= G185) mutation to E: In gsm2-1; loss of activity and lack of C6, C7 and C8 aliphatic glucosinolates.
Query Sequence
>Pf6N2E2_1040 FitnessBrowser__pseudo6_N2E2:Pf6N2E2_1040
MNHKNNVDILISEVGPRDGLQSVSATMPTELKLKWLTALADAGLREIEVGSFVSPKLLPQ
MADAAELVMHLRKRPDVFVTALVPNLKGAEAAFNAGVQKITLPISVSEPHSLANIRKTHQ
QVFDEVRAVIALRNERFAHVEVESGLSTVFGCTIQGEVPEDDVIRMALIMAELGVDEVGL
ADTVGYANPAQVRRVFTRLRNEIGSKAGSAHFHNTRGQGLANVVAALDVGVTTIDASQGG
IGGCPYAPGASGNIVTEDLVYLLESMDLRTGVDIDKLVAAREWLMQGLPGEPLYGFIPDA
GVGKNFHYAGGAR
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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