SitesBLAST

Comparing BPHYT_RS03930 FitnessBrowser__BFirm:BPHYT_RS03930 to proteins with known functional sites using BLASTp with E ≤ 0.001.

Found 20 (the maximum) hits to proteins with known functional sites

6ndsA Structure of an hmg-coa lyase from acenitobacter baumannii in complex with coenzyme a and 3-methylmalate
39% identity, 94% coverage: 1:304/325 of query aligns to 1:296/305 of 6ndsA

• binding coenzyme a: V52 (= V52), S53 (≠ P53), I57 (≠ L57), N84 (= N84), G87 (= G87), R90 (= R90), N113 (= N113), M114 (≠ V114), R115 (= R115)
• binding zinc ion: D17 (= D17), H207 (= H214), H209 (= H216)

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)
36% identity, 90% coverage: 1:291/325 of query aligns to 26:310/325 of P35914

• E37 (= E12) to K: in HMGCLD; activity lower than 5% respect to the wild-type; mutation to D: Normal activity.
• R41 (= R16) to Q: in HMGCLD; loss of activity and of proton exchange; dbSNP:rs121964997; mutation to M: Reduced activity, and loss of proton exchange.
• D42 (= D17) 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 (≠ A23) 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 (= C155) to Y: in HMGCLD; activity lower than 5% respect to the wild-type; dbSNP:rs765475941
• F192 (≠ A173) to S: in HMGCLD; activity lower than 5% respect to the wild-type
• I200 (= I181) to F: in HMGCLD; activity lower than 5% respect to the wild-type
• G203 (= G184) to E: in HMGCLD; complete loss of activity; dbSNP:rs1553131940
• D204 (= D185) mutation to A: Reduced activity, and reduced affinity for metal cofactor and substrate.
• H233 (= H214) to R: in HMGCLD; loss of activity; dbSNP:rs727503963; mutation to A: Loss of activity, and reduced proton exchange rate.
• E279 (= E260) mutation to A: Reduced thermal stability, but normal activity.
• D280 (= D261) 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)
36% identity, 89% coverage: 4:291/325 of query aligns to 2:283/296 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 (= R16), D15 (= D17), Q18 (= Q20), F49 (= F51), V50 (= V52), S51 (≠ P53), W54 (≠ L56), P81 (= P83), N82 (= N84), K84 (= K86), G85 (= G87), N111 (= N113), R122 (≠ A124), Y140 (≠ G148), S142 (= S150), T178 (= T186), H206 (= H214)
• binding magnesium ion: D15 (= D17), H206 (= H214), H208 (= H216)

2cw6A Crystal structure of human hmg-coa lyase: insights into catalysis and the molecular basis for hydroxymethylglutaric aciduria (see paper)
36% identity, 89% coverage: 4:291/325 of query aligns to 2:283/296 of 2cw6A

• binding 3-hydroxypentanedioic acid: Q18 (= Q20), F100 (≠ P102)
• binding magnesium ion: D15 (= D17), H206 (= H214), H208 (= H216), N248 (= N256)

3mp5B Crystal structure of human lyase r41m in complex with hmg-coa (see paper)
35% identity, 89% coverage: 4:291/325 of query aligns to 2:283/296 of 3mp5B

• binding 3-hydroxy-3-methylglutaryl-coenzyme a: D15 (= D17), Q18 (= Q20), S51 (≠ P53), W54 (≠ L56), F100 (≠ P102), N111 (= N113), N113 (≠ R115), Y140 (≠ G148), S142 (= S150), T178 (= T186), C239 (= C247)
• binding magnesium ion: D15 (= D17), H206 (= H214), H208 (= H216)

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)
34% identity, 90% coverage: 1:291/325 of query aligns to 71:355/370 of Q8TB92

• R86 (= R16) mutation to Q: Abolishes catalytic activity.
• L237 (≠ A173) mutation to S: Abolishes catalytic activity.
• H278 (= H214) 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)
40% identity, 85% coverage: 6:280/325 of query aligns to 2:270/283 of 1ydnA

• binding calcium ion: D13 (= D17), H204 (= H214), H206 (= H216), N246 (= N256)

P13703 Hydroxymethylglutaryl-CoA lyase; HL; HMG-CoA lyase; 3-hydroxy-3-methylglutarate-CoA lyase; EC 4.1.3.4 from Pseudomonas mevalonii (see paper)
38% identity, 83% coverage: 8:278/325 of query aligns to 4:268/301 of P13703

• C237 (= C247) active site

3rmjB Crystal structure of truncated alpha-isopropylmalate synthase from neisseria meningitidis (see paper)
29% identity, 89% coverage: 7:296/325 of query aligns to 3:280/308 of 3rmjB

• active site: Q16 (= Q20)
• binding manganese (ii) ion: D13 (= D17), H201 (= H214), H203 (= H216), N237 (= N256)

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)
29% identity, 89% coverage: 7:296/325 of query aligns to 6:283/517 of Q9JZG1

• D16 (= D17) binding
• H204 (= H214) binding
• H206 (= H216) binding
• N240 (= N256) 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)
36% identity, 25% coverage: 165:245/325 of query aligns to 176:255/418 of Q9Y823

• T197 (= T186) 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 (≠ H211) mutation to Q: Does not affect the catalytic activity but impairs L-lysine inhibition.
• H224 (= H214) binding ; binding
• H226 (= H216) binding ; binding

Sites not aligning to the query:

• 43 binding ; mutation R->A,K,Q: Abolishes the catalytic activity.
• 44 binding ; binding ; binding
• 47 Q→A: Abolishes the catalytic activity.
• 74 E→A: Abolishes the catalytic activity.; E→Q: Results in a moderate decrease in the turnover number and a slight increase in the Km value for each substrate.
• 103 binding ; H→A: Substantially impairs catalytic efficiency.
• 123 binding ; D→N: Does not affect the catalytic activity but impairs L-lysine inhibition.
• 163 binding ; mutation R->A,Q: Abolishes the catalytic activity.; R→K: Severely diminishes affinity for 2-oxoglutarate and substantially impairs catalytic efficiency.
• 165 binding ; S→A: Results in a moderate decrease in catalytic efficiency.
• 167 mutation E->A,Q: Abolishes the catalytic activity.
• 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.

3ivtB Homocitrate synthase lys4 bound to 2-og (see paper)
36% identity, 25% coverage: 165:245/325 of query aligns to 171:250/400 of 3ivtB

• binding 2-oxoglutaric acid: T192 (= T186), H219 (= H214), H221 (= H216)
• binding zinc ion: H219 (= H214), H221 (= H216)

Sites not aligning to the query:

• active site: 42
• binding 2-oxoglutaric acid: 38, 98, 158, 160
• binding zinc ion: 39

3ivsA Homocitrate synthase lys4 (see paper)
36% identity, 25% coverage: 165:245/325 of query aligns to 140:219/364 of 3ivsA

• binding cobalt (ii) ion: H188 (= H214), H190 (= H216)

Sites not aligning to the query:

• active site: 24
• binding cobalt (ii) ion: 21

3mi3A Homocitrate synthase lys4 bound to lysine (see paper)
36% identity, 25% coverage: 165:245/325 of query aligns to 142:221/370 of 3mi3A

• binding lysine: T163 (= T186), H190 (= H214), H192 (= H216)
• binding zinc ion: H190 (= H214), H192 (= H216)

Sites not aligning to the query:

• active site: 24
• binding lysine: 20, 100
• binding zinc ion: 21

Q9FG67 Methylthioalkylmalate synthase 1, chloroplastic; 2-isopropylmalate synthase 3; EC 2.3.3.17 from Arabidopsis thaliana (Mouse-ear cress) (see paper)
25% identity, 63% coverage: 85:289/325 of query aligns to 177:367/506 of Q9FG67

• A290 (≠ S212) 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.

2nx9B Crystal structure of the carboxyltransferase domain of the oxaloacetate decarboxylase na+ pump from vibrio cholerae (see paper)
33% identity, 34% coverage: 169:280/325 of query aligns to 162:266/453 of 2nx9B

• active site: K177 (≠ G184), H206 (= H214), H208 (= H216)
• binding zinc ion: H206 (= H214), H208 (= H216)

Sites not aligning to the query:

• active site: 16, 19, 120, 341
• binding zinc ion: 16

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, 66% coverage: 85:298/325 of query aligns to 177:381/503 of Q9FN52

• G263 (= G188) mutation to E: In gsm2-1; loss of activity and lack of C6, C7 and C8 aliphatic glucosinolates.

6e1jA Crystal structure of methylthioalkylmalate synthase (bjumam1.1) from brassica juncea (see paper)
25% identity, 62% coverage: 98:298/325 of query aligns to 117:314/409 of 6e1jA

• binding coenzyme a: F121 (≠ P102), K132 (≠ N113), L133 (≠ V114)
• binding 4-(methylsulfanyl)-2-oxobutanoic acid: P192 (≠ G184), T194 (= T186), H225 (= H214), H227 (= H216)
• binding manganese (ii) ion: H225 (= H214), H227 (= H216)

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

O87198 Homocitrate synthase; HCS; EC 2.3.3.14 from Thermus thermophilus (strain ATCC BAA-163 / DSM 7039 / HB27) (see paper)
28% identity, 82% coverage: 15:282/325 of query aligns to 11:266/376 of O87198

• R12 (= R16) binding
• E13 (≠ D17) binding
• H72 (≠ A80) 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 (≠ V100) binding
• R133 (≠ I146) binding
• S135 (≠ G148) binding
• T166 (= T186) binding ; binding
• H195 (= H214) binding
• H197 (= H216) binding

2zyfA Crystal structure of homocitrate synthase from thermus thermophilus complexed with magnesuim ion and alpha-ketoglutarate (see paper)
27% identity, 82% coverage: 15:282/325 of query aligns to 11:260/314 of 2zyfA