SitesBLAST
Comparing Echvi_3855 FitnessBrowser__Cola:Echvi_3855 to proteins with known functional sites using BLASTp with E ≤ 0.001.
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Found 19 hits to proteins with known functional sites (download)
1ydnA Crystal structure of the hmg-coa lyase from brucella melitensis, northeast structural genomics target lr35. (see paper)
30% identity, 94% coverage: 8:272/281 of query aligns to 12:273/283 of 1ydnA
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)
32% identity, 97% coverage: 1:272/281 of query aligns to 78:347/370 of Q8TB92
- R86 (= R8) mutation to Q: Abolishes catalytic activity.
- L237 (= L161) mutation to S: Abolishes catalytic activity.
- H278 (= H202) 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.
3mp3B Crystal structure of human lyase in complex with inhibitor hg-coa (see paper)
31% identity, 97% coverage: 1:272/281 of query aligns to 6:275/296 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 (= R8), D15 (= D9), Q18 (= Q12), F49 (= F43), V50 (= V44), S51 (= S45), W54 (≠ A48), P81 (≠ A76), N82 (= N77), K84 (≠ R79), G85 (= G80), N111 (= N107), R122 (≠ V118), Y140 (= Y136), S142 (= S138), T178 (= T174), H206 (= H202)
- binding magnesium ion: D15 (= D9), H206 (= H202), H208 (= H204)
2cw6A Crystal structure of human hmg-coa lyase: insights into catalysis and the molecular basis for hydroxymethylglutaric aciduria (see paper)
31% identity, 97% coverage: 1:272/281 of query aligns to 6:275/296 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)
31% identity, 97% coverage: 1:272/281 of query aligns to 33:302/325 of P35914
- E37 (= E5) to K: in HMGCLD; activity lower than 5% respect to the wild-type; mutation to D: Normal activity.
- R41 (= R8) to Q: in HMGCLD; loss of activity and of proton exchange; dbSNP:rs121964997; mutation to M: Reduced activity, and loss of proton exchange.
- D42 (= D9) 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 (≠ E15) to N: in HMGCLD; abolishes almost all enzymatic activity
- E72 (≠ D39) mutation to A: Loss of activity, and reduced affinity for metal cofactor and substrate.
- S142 (= S111) to F: in HMGCLD; activity lower than 5% respect to the wild-type
- C174 (≠ N143) to Y: in HMGCLD; activity lower than 5% respect to the wild-type; dbSNP:rs765475941
- F192 (≠ L161) to S: in HMGCLD; activity lower than 5% respect to the wild-type
- I200 (= I169) to F: in HMGCLD; activity lower than 5% respect to the wild-type
- G203 (≠ S172) to E: in HMGCLD; complete loss of activity; dbSNP:rs1553131940
- D204 (= D173) mutation to A: Reduced activity, and reduced affinity for metal cofactor and substrate.
- H233 (= H202) to R: in HMGCLD; loss of activity; dbSNP:rs727503963; mutation to A: Loss of activity, and reduced proton exchange rate.
- E279 (= E249) mutation to A: Reduced thermal stability, but normal activity.
- D280 (≠ A250) 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)
30% identity, 97% coverage: 1:272/281 of query aligns to 6:275/296 of 3mp5B
- binding 3-hydroxy-3-methylglutaryl-coenzyme a: D15 (= D9), Q18 (= Q12), S51 (= S45), W54 (≠ A48), F100 (≠ L93), N111 (= N107), N113 (= N109), Y140 (= Y136), S142 (= S138), T178 (= T174), C239 (= C235)
- binding magnesium ion: D15 (= D9), H206 (= H202), H208 (= H204)
P13703 Hydroxymethylglutaryl-CoA lyase; HL; HMG-CoA lyase; 3-hydroxy-3-methylglutarate-CoA lyase; EC 4.1.3.4 from Pseudomonas mevalonii (see paper)
32% identity, 89% coverage: 1:249/281 of query aligns to 4:250/301 of P13703
- C237 (= C235) active site
6ndsA Structure of an hmg-coa lyase from acenitobacter baumannii in complex with coenzyme a and 3-methylmalate
32% identity, 90% coverage: 7:259/281 of query aligns to 15:263/305 of 6ndsA
- binding coenzyme a: V52 (= V44), S53 (= S45), I57 (≠ M49), N84 (= N77), G87 (= G80), R90 (≠ D83), N113 (= N107), M114 (≠ T108), R115 (≠ N109)
- binding zinc ion: D17 (= D9), H207 (= H202), H209 (= H204)
2nx9B Crystal structure of the carboxyltransferase domain of the oxaloacetate decarboxylase na+ pump from vibrio cholerae (see paper)
33% identity, 38% coverage: 160:265/281 of query aligns to 165:262/453 of 2nx9B
Sites not aligning to the query:
3bliA Crystal structure of the catalytic domain of licms in complexed with pyruvate and acetyl-coa (see paper)
30% identity, 50% coverage: 137:277/281 of query aligns to 142:270/311 of 3bliA
Sites not aligning to the query:
Q8F3Q1 (R)-citramalate synthase CimA; LiCMS; EC 2.3.3.21 from Leptospira interrogans serogroup Icterohaemorrhagiae serovar Lai (strain 56601) (see 2 papers)
30% identity, 50% coverage: 137:277/281 of query aligns to 148:276/516 of Q8F3Q1
- T179 (= T174) binding ; mutation to A: 16.4-fold increase in Km for pyruvate and 186-fold decrease in kcat.
Sites not aligning to the query:
- 16 mutation R->K,Q: Loss of activity.
- 16:17 binding
- 17 D→A: 34-fold increase in Km for pyruvate and 315-fold decrease in kcat.; D→N: 4.4-fold increase in Km for pyruvate and 480-fold decrease in kcat.
- 81 L→A: 4.7-fold increase in Km for pyruvate and 15.7-fold decrease in kcat.; L→V: 3.3-fold increase in Km for pyruvate and 10.1-fold decrease in kcat.
- 83 F→A: 5-fold increase in Km for acetyl-CoA and 120-fold decrease in kcat.
- 104 L→V: 1.8-fold increase in Km for pyruvate and 3.4-fold decrease in kcat.
- 144 binding ; Y→L: 259-fold increase in Km for pyruvate and 76-fold decrease in kcat.; Y→V: 114-fold increase in Km for pyruvate and 5.3-fold decrease in kcat.
- 146 mutation E->D,Q: Minor effects on the binding of acetyl-CoA, but causes a strong decrease in kcat.
- 302 mutation H->A,N: Loss of activity.
- 304 D→A: 5.2-fold increase in Km for acetyl-CoA and 16.6-fold decrease in kcat.
- 310 N→A: 2.2-fold increase in Km for acetyl-CoA and 1.7-fold decrease in kcat.
- 311 L→A: 8-fold increase in Km for acetyl-CoA and 6-fold decrease in kcat.
- 312 Y→A: Loss of activity.
- 430 Y→L: No change in Km for acetyl-CoA and 2.3-fold decrease in kcat. Severely impairs inhibition by isoleucine.
- 431 D→A: 1.8-fold decrease in Km for acetyl-CoA and 5-fold decrease in kcat.
- 451 L→V: 1.5-fold increase in Km for acetyl-CoA and 4.3 decrease in kcat.
- 454 Y→A: 1.4 decrease in Km for acetyl-CoA and 17-fold decrease in kcat. Still inhibited by isoleucine and weakly inhibited by leucine.
- 458 I→A: 1.3-fold decrease in Km for acetyl-CoA and 14-fold decrease in kcat. Abolishes inhibition by isoleucine.
- 464 T→A: 1.8-fold decrease in Km for acetyl-CoA and 4.3-fold decrease in kcat.
- 468 V→A: No change in Km for acetyl-CoA and 2-fold decrease in kcat. Increases inhibition by isoleucine and leucine becomes an effective inhibitor.
- 493 P→A: 1.5-fold decrease in Km for acetyl-CoA and 2.6-fold decrease in kcat.
- 495 Q→A: 1.6-fold decrease in Km for acetyl-CoA and 2.8-fold decrease in kcat.
3ivtB Homocitrate synthase lys4 bound to 2-og (see paper)
24% identity, 80% coverage: 8:233/281 of query aligns to 38:250/400 of 3ivtB
Q9Y823 Homocitrate synthase, mitochondrial; HCS; EC 2.3.3.14 from Schizosaccharomyces pombe (strain 972 / ATCC 24843) (Fission yeast) (see 2 papers)
24% identity, 82% coverage: 3:233/281 of query aligns to 37:255/418 of Q9Y823
- R43 (= R8) binding ; mutation R->A,K,Q: Abolishes the catalytic activity.
- E44 (≠ D9) binding ; binding ; binding
- Q47 (= Q12) mutation to A: Abolishes the catalytic activity.
- E74 (≠ S42) 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 (vs. gap) binding ; mutation to A: Substantially impairs catalytic efficiency.
- D123 (≠ G94) binding ; mutation to N: Does not affect the catalytic activity but impairs L-lysine inhibition.
- R163 (≠ G140) binding ; mutation R->A,Q: Abolishes the catalytic activity.; mutation to K: Severely diminishes affinity for 2-oxoglutarate and substantially impairs catalytic efficiency.
- S165 (≠ G142) binding ; mutation to A: Results in a moderate decrease in catalytic efficiency.
- E167 (≠ P144) mutation E->A,Q: Abolishes the catalytic activity.
- T197 (= T174) 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 (≠ G200) mutation to Q: Does not affect the catalytic activity but impairs L-lysine inhibition.
- H224 (= H202) binding ; binding
- H226 (= H204) 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.
3rmjB Crystal structure of truncated alpha-isopropylmalate synthase from neisseria meningitidis (see paper)
25% identity, 46% coverage: 152:279/281 of query aligns to 148:275/308 of 3rmjB
Sites not aligning to the query:
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, 57% coverage: 74:233/281 of query aligns to 91:247/399 of 6ktqA
- binding 2-oxoglutaric acid: R154 (≠ G140), T156 (≠ G142), E158 (≠ P144), S184 (≠ A170), T188 (= T174), H216 (= H202), H218 (= H204)
- binding coenzyme a: R96 (= R79), A97 (≠ G80), F116 (≠ P96), H128 (≠ T108), E158 (≠ P144)
- binding zinc ion: H216 (= H202), H218 (= H204)
Sites not aligning to the query:
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, 46% coverage: 152:279/281 of query aligns to 151:278/517 of Q9JZG1
- H204 (= H202) binding
- H206 (= H204) binding
- N240 (= N245) binding
Sites not aligning to the query:
- 16 binding
- 366:517 Required for the condensation reaction. Not required to bind substrate
3ivsA Homocitrate synthase lys4 (see paper)
26% identity, 80% coverage: 8:233/281 of query aligns to 20:219/364 of 3ivsA
3mi3A Homocitrate synthase lys4 bound to lysine (see paper)
26% identity, 82% coverage: 3:233/281 of query aligns to 14:221/370 of 3mi3A
Q9FG67 Methylthioalkylmalate synthase 1, chloroplastic; 2-isopropylmalate synthase 3; EC 2.3.3.17 from Arabidopsis thaliana (Mouse-ear cress) (see paper)
22% identity, 67% coverage: 71:259/281 of query aligns to 158:342/506 of Q9FG67
- A290 (≠ G200) 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
>Echvi_3855 FitnessBrowser__Cola:Echvi_3855
MKIIECPRDAMQGREVFIDTAIKAAYINQLLNVGFDTVDFGSFVSPKAMPQMRDTAEVLD
LLDLFHSKSKLLAIVANVRGAEDAMQFEEIDYLGFPLSISETFQQRNTNKSIQEALEVVA
NLQNMCEVKGRTLVTYLSMGFGNPYGEPFSADLVAEFVGKLDELGVKVIALSDTIGAADP
ALIEEVFKTNTQAYPEIEFGGHFHSRAEHIAEKVEAGLRGGCRRFDGAINGFGGCPMAKD
ELVGNVATEALIEVLEKNGYDLGMNQEEFGEAMKLAKFVFQ
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