SitesBLAST
Comparing GFF2610 FitnessBrowser__psRCH2:GFF2610 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
55% identity, 96% coverage: 5:303/311 of query aligns to 8:305/305 of 6ndsA
- binding coenzyme a: V52 (≠ T49), S53 (= S50), I57 (= I54), N84 (= N81), G87 (= G84), R90 (= R87), N113 (= N110), M114 (≠ L111), R115 (= R112)
- binding zinc ion: D17 (= D14), H207 (= H205), H209 (= H207)
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)
42% identity, 86% coverage: 7:273/311 of query aligns to 80:346/370 of Q8TB92
- R86 (= R13) mutation to Q: Abolishes catalytic activity.
- L237 (= L164) mutation to S: Abolishes catalytic activity.
- H278 (= H205) 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.
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)
38% identity, 94% coverage: 3:293/311 of query aligns to 31:321/325 of P35914
- E37 (= E9) to K: in HMGCLD; activity lower than 5% respect to the wild-type; mutation to D: Normal activity.
- R41 (= R13) to Q: in HMGCLD; loss of activity and of proton exchange; dbSNP:rs121964997; mutation to M: Reduced activity, and loss of proton exchange.
- D42 (= D14) 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 (≠ A20) to N: in HMGCLD; abolishes almost all enzymatic activity
- E72 (= E44) mutation to A: Loss of activity, and reduced affinity for metal cofactor and substrate.
- S142 (≠ T114) to F: in HMGCLD; activity lower than 5% respect to the wild-type
- C174 (= C146) to Y: in HMGCLD; activity lower than 5% respect to the wild-type; dbSNP:rs765475941
- F192 (≠ L164) to S: in HMGCLD; activity lower than 5% respect to the wild-type
- I200 (= I172) to F: in HMGCLD; activity lower than 5% respect to the wild-type
- G203 (≠ C175) to E: in HMGCLD; complete loss of activity; dbSNP:rs1553131940
- D204 (= D176) mutation to A: Reduced activity, and reduced affinity for metal cofactor and substrate.
- H233 (= H205) to R: in HMGCLD; loss of activity; dbSNP:rs727503963; mutation to A: Loss of activity, and reduced proton exchange rate.
- E279 (= E251) mutation to A: Reduced thermal stability, but normal activity.
- D280 (= D252) 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)
38% identity, 94% coverage: 3:293/311 of query aligns to 4:294/296 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 (= R13), D15 (= D14), Q18 (= Q17), F49 (= F48), V50 (≠ T49), S51 (= S50), W54 (≠ A53), P81 (= P80), N82 (= N81), K84 (= K83), G85 (= G84), N111 (= N110), R122 (≠ Q121), Y140 (≠ S139), S142 (= S141), T178 (= T177), H206 (= H205)
- binding magnesium ion: D15 (= D14), H206 (= H205), H208 (= H207)
2cw6A Crystal structure of human hmg-coa lyase: insights into catalysis and the molecular basis for hydroxymethylglutaric aciduria (see paper)
38% identity, 94% coverage: 3:293/311 of query aligns to 4:294/296 of 2cw6A
3mp5B Crystal structure of human lyase r41m in complex with hmg-coa (see paper)
38% identity, 94% coverage: 3:293/311 of query aligns to 4:294/296 of 3mp5B
- binding 3-hydroxy-3-methylglutaryl-coenzyme a: D15 (= D14), Q18 (= Q17), S51 (= S50), W54 (≠ A53), F100 (≠ V99), N111 (= N110), N113 (≠ R112), Y140 (≠ S139), S142 (= S141), T178 (= T177), C239 (= C238)
- binding magnesium ion: D15 (= D14), H206 (= H205), H208 (= H207)
1ydnA Crystal structure of the hmg-coa lyase from brucella melitensis, northeast structural genomics target lr35. (see paper)
44% identity, 86% coverage: 3:271/311 of query aligns to 2:270/283 of 1ydnA
P13703 Hydroxymethylglutaryl-CoA lyase; HL; HMG-CoA lyase; 3-hydroxy-3-methylglutarate-CoA lyase; EC 4.1.3.4 from Pseudomonas mevalonii (see paper)
36% identity, 88% coverage: 9:283/311 of query aligns to 8:282/301 of P13703
- C237 (= C238) active site
6ktqA Crystal structure of catalytic domain of homocitrate synthase from sulfolobus acidocaldarius (sahcs(dram)) in complex with alpha- ketoglutarate/zn2+/coa (see paper)
24% identity, 76% coverage: 1:236/311 of query aligns to 18:247/399 of 6ktqA
- binding 2-oxoglutaric acid: R30 (= R13), R154 (≠ N137), T156 (≠ S139), E158 (≠ S141), S184 (≠ T173), T188 (= T177), H216 (= H205), H218 (= H207)
- binding coenzyme a: V67 (≠ A53), R96 (≠ K83), A97 (≠ G84), F116 (≠ V99), H128 (≠ L111), E158 (≠ S141)
- binding zinc ion: E31 (≠ D14), H216 (= H205), H218 (= H207)
3rmjB Crystal structure of truncated alpha-isopropylmalate synthase from neisseria meningitidis (see paper)
23% identity, 91% coverage: 4:286/311 of query aligns to 3:280/308 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)
23% identity, 91% coverage: 4:286/311 of query aligns to 6:283/517 of Q9JZG1
- D16 (= D14) binding
- H204 (= H205) binding
- H206 (= H207) binding
- N240 (= N247) binding
Sites not aligning to the query:
- 366:517 Required for the condensation reaction. Not required to bind substrate
Q8F3Q1 (R)-citramalate synthase CimA; LiCMS; EC 2.3.3.21 from Leptospira interrogans serogroup Icterohaemorrhagiae serovar Lai (strain 56601) (see 2 papers)
26% identity, 75% coverage: 4:236/311 of query aligns to 7:238/516 of Q8F3Q1
- R16 (= R13) mutation R->K,Q: Loss of activity.
- RD 16:17 (= RD 13:14) binding
- D17 (= D14) mutation to A: 34-fold increase in Km for pyruvate and 315-fold decrease in kcat.; mutation to N: 4.4-fold increase in Km for pyruvate and 480-fold decrease in kcat.
- L81 (≠ T76) mutation to A: 4.7-fold increase in Km for pyruvate and 15.7-fold decrease in kcat.; mutation to V: 3.3-fold increase in Km for pyruvate and 10.1-fold decrease in kcat.
- F83 (≠ L78) mutation to A: 5-fold increase in Km for acetyl-CoA and 120-fold decrease in kcat.
- L104 (≠ V99) mutation to V: 1.8-fold increase in Km for pyruvate and 3.4-fold decrease in kcat.
- Y144 (≠ S139) binding ; mutation to L: 259-fold increase in Km for pyruvate and 76-fold decrease in kcat.; mutation to V: 114-fold increase in Km for pyruvate and 5.3-fold decrease in kcat.
- E146 (≠ S141) mutation E->D,Q: Minor effects on the binding of acetyl-CoA, but causes a strong decrease in kcat.
- T179 (= T177) binding ; mutation to A: 16.4-fold increase in Km for pyruvate and 186-fold decrease in kcat.
Sites not aligning to the query:
- 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.
3bliA Crystal structure of the catalytic domain of licms in complexed with pyruvate and acetyl-coa (see paper)
26% identity, 75% coverage: 4:236/311 of query aligns to 1:232/311 of 3bliA
2nx9B Crystal structure of the carboxyltransferase domain of the oxaloacetate decarboxylase na+ pump from vibrio cholerae (see paper)
32% identity, 38% coverage: 159:276/311 of query aligns to 161:271/453 of 2nx9B
Sites not aligning to the query:
3mi3A Homocitrate synthase lys4 bound to lysine (see paper)
28% identity, 74% coverage: 7:236/311 of query aligns to 14:221/370 of 3mi3A
Q9Y823 Homocitrate synthase, mitochondrial; HCS; EC 2.3.3.14 from Schizosaccharomyces pombe (strain 972 / ATCC 24843) (Fission yeast) (see 2 papers)
28% identity, 74% coverage: 7:236/311 of query aligns to 37:255/418 of Q9Y823
- R43 (= R13) binding ; mutation R->A,K,Q: Abolishes the catalytic activity.
- E44 (≠ D14) binding ; binding ; binding
- Q47 (= Q17) mutation to A: Abolishes the catalytic activity.
- E74 (= E44) 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 (≠ P80) binding ; mutation to A: Substantially impairs catalytic efficiency.
- D123 (≠ N97) binding ; mutation to N: Does not affect the catalytic activity but impairs L-lysine inhibition.
- R163 (≠ N137) binding ; mutation R->A,Q: Abolishes the catalytic activity.; mutation to K: Severely diminishes affinity for 2-oxoglutarate and substantially impairs catalytic efficiency.
- S165 (= S139) binding ; mutation to A: Results in a moderate decrease in catalytic efficiency.
- E167 (≠ S141) mutation E->A,Q: Abolishes the catalytic activity.
- T197 (= T177) 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 (≠ T203) mutation to Q: Does not affect the catalytic activity but impairs L-lysine inhibition.
- H224 (= H205) binding ; binding
- H226 (= H207) 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.
3ivtB Homocitrate synthase lys4 bound to 2-og (see paper)
28% identity, 74% coverage: 7:236/311 of query aligns to 32:250/400 of 3ivtB
3ivsA Homocitrate synthase lys4 (see paper)
27% identity, 74% coverage: 7:236/311 of query aligns to 14:219/364 of 3ivsA
O87198 Homocitrate synthase; HCS; EC 2.3.3.14 from Thermus thermophilus (strain ATCC BAA-163 / DSM 7039 / HB27) (see paper)
26% identity, 88% coverage: 13:287/311 of query aligns to 12:274/376 of O87198
- R12 (= R13) binding
- E13 (≠ D14) binding
- H72 (≠ P80) 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 (≠ N97) binding
- R133 (≠ S139) binding
- S135 (= S141) binding
- T166 (= T177) binding ; binding
- H195 (= H205) binding
- H197 (= H207) binding
Q53WI0 4-hydroxy-2-oxovalerate aldolase; HOA; 4-hydroxy-2-keto-pentanoic acid aldolase; 4-hydroxy-2-oxohexanoate aldolase; 4-hydroxy-2-oxopentanoate aldolase; EC 4.1.3.39; EC 4.1.3.43 from Thermus thermophilus (strain ATCC 27634 / DSM 579 / HB8) (see paper)
32% identity, 36% coverage: 163:275/311 of query aligns to 158:265/347 of Q53WI0
Sites not aligning to the query:
- 324 A→G: Increases the channeling efficiency of propanaldehyde from 57% to 94%.
Query Sequence
>GFF2610 FitnessBrowser__psRCH2:GFF2610
MNKRLYIQEVATRDGFQIEADFVPTEAKIALIDRLSQTGLAKIEVTSFTSPKAIPNLRDA
EDVMRGIRRVEGVEYTVLVPNVKGCERALACEVDEINLVMSASDTHGLANLRMTPEQSLV
QFREIIEVTRGSGVFINASLSTTFGCPFEGDVPERRIYELVQRLLEIGVQGITLCDTTGM
ADPAQVERICHEVLNSWPQAVFTAHFHNTRGMGLANALAALNAGIDRFDASLGGLGGCPY
APGASGNICTEDLVHMFQRMGLNTGVDLDRLLQCAADLPQLVGHDVPGAVLKAGKADRRY
PKPKWMQEAGV
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