DB code: D00867
RLCP classification | 3.1177.220080.38 : Transfer | |
---|---|---|
5.115.129300.66 : Elimination | ||
3.1197.15020.136 : Transfer | ||
CATH domain | 3.40.47.10 : Peroxisomal Thiolase; Chain A, domain 1 | Catalytic domain |
3.40.47.10 : Peroxisomal Thiolase; Chain A, domain 1 | Catalytic domain | |
E.C. | 2.3.1.180 | |
CSA | ||
M-CSA | ||
MACiE |
CATH domain | Related DB codes (homologues) |
---|---|
3.40.47.10 : Peroxisomal Thiolase; Chain A, domain 1 | D00090 D00411 D00509 D00825 D00826 D00871 |
Uniprot Enzyme Name | UniprotKB | Protein name | Synonyms | RefSeq | Pfam |
---|---|---|---|---|
O67185 |
3-oxoacyl-[acyl-carrier-protein] synthase 3
|
EC
2.3.1.180
3-oxoacyl-[acyl-carrier-protein] synthase III Beta-ketoacyl-ACP synthase III KAS III |
NP_213748.1
(Protein)
NC_000918.1 (DNA/RNA sequence) |
PF08545
(ACP_syn_III)
PF08541 (ACP_syn_III_C) [Graphical View] |
Q820T1 |
3-oxoacyl-[acyl-carrier-protein] synthase 3
|
EC
2.3.1.180
3-oxoacyl-[acyl-carrier-protein] synthase III Beta-ketoacyl-ACP synthase III KAS III |
NP_816505.1
(Protein)
NC_004668.1 (DNA/RNA sequence) |
PF08545
(ACP_syn_III)
PF08541 (ACP_syn_III_C) [Graphical View] |
KEGG enzyme name |
---|
Beta-ketoacyl-acyl-carrier-protein synthase III
3-Oxoacyl:ACP synthase III 3-Ketoacyl-acyl carrier protein synthase III KASIII KAS III FabH Beta-ketoacyl-acyl carrier protein synthase III Beta-ketoacyl-ACP synthase III Beta-ketoacyl (acyl carrier protein) synthase III Beta-ketoacyl-[acyl-carrier-protein] synthase III Acetyl-CoA:malonyl-[acyl-carrier-protein] C-acyltransferase |
UniprotKB: Accession Number | Entry name | Activity | Subunit | Subcellular location | Cofactor |
---|---|---|---|---|---|
O67185 | FABH_AQUAE | Acetyl-CoA + malonyl-[acyl-carrier-protein] = acetoacyl-[acyl-carrier-protein] + CoA + CO2. | Homodimer (By similarity). | Cytoplasm (Probable). | |
Q820T1 | FABH_ENTFA | Acetyl-CoA + malonyl-[acyl-carrier-protein] = acetoacyl-[acyl-carrier-protein] + CoA + CO2. | Homodimer (By similarity). | Cytoplasm (Probable). |
KEGG Pathways | Map code | Pathways | E.C. |
---|---|---|
MAP00061 | Fatty acid biosynthesis |
Compound table | ||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Substrates | Products | Intermediates | ||||||||||||
KEGG-id | C00024 | C01209 | C05744 | C00010 | C00011 | I00132 | I00133 | I00134 | I00135 | |||||
E.C. | ||||||||||||||
Compound | acetyl-CoA | malonyl-[acyl-carrier protein] | acetoacetyl-[acyl-carrier protein] | CoA | CO2 | Peptidyl-Cys-tetrahedral-acetyl-CoA | Peptidyl-Cys-S-acetyl | [Acyl-carrier protein]-decarboxylated malonyl group (Peptidyl-Ser-phosphopantetheine-S-enolate) | Peptidyl-Cys-tetrahedral-acetyl-keto-[acyl-carrier protein] | |||||
Type | amine group,carbohydrate,nucleotide ,peptide/protein,sulfide group | carbohydrate,carboxyl group,peptide/protein,phosphate group/phosphate ion,sulfide group | carbohydrate,peptide/protein,phosphate group/phosphate ion,sulfide group | amine group,carbohydrate,nucleotide ,peptide/protein,sulfhydryl group | others | |||||||||
ChEBI |
15351 15351 |
15346 15346 |
16526 16526 |
|||||||||||
PubChem |
444493 6302 444493 6302 |
6816 87642 6816 87642 |
280 280 |
|||||||||||
2ebdA01 | Unbound | Unbound | Unbound | Unbound | Unbound | Unbound | Unbound | Unbound | Unbound | |||||
2ebdB01 | Unbound | Unbound | Unbound | Unbound | Unbound | Unbound | Unbound | Unbound | Unbound | |||||
3il4A01 | Bound:ACO | Unbound | Unbound | Unbound | Unbound | Unbound | Unbound | Unbound | Unbound | |||||
3il4B01 | Bound:ACO | Unbound | Unbound | Unbound | Unbound | Unbound | Unbound | Unbound | Unbound | |||||
3il4C01 | Bound:ACO | Unbound | Unbound | Unbound | Unbound | Unbound | Unbound | Unbound | Unbound | |||||
3il4D01 | Bound:ACO | Unbound | Unbound | Unbound | Unbound | Unbound | Unbound | Unbound | Unbound | |||||
3il5A01 | Unbound | Unbound | Unbound | Unbound | Unbound | Unbound | Unbound | Unbound | Unbound | |||||
3il5B01 | Unbound | Unbound | Unbound | Unbound | Unbound | Unbound | Unbound | Unbound | Unbound | |||||
3il5C01 | Unbound | Unbound | Unbound | Unbound | Unbound | Unbound | Unbound | Unbound | Unbound | |||||
3il5D01 | Unbound | Unbound | Unbound | Unbound | Unbound | Unbound | Unbound | Unbound | Unbound | |||||
3il6A01 | Unbound | Unbound | Unbound | Unbound | Unbound | Unbound | Intermediate-bound:SCY | Unbound | Unbound | |||||
2ebdA02 | Unbound | Unbound | Unbound | Unbound | Unbound | Unbound | Unbound | Unbound | Unbound | |||||
2ebdB02 | Unbound | Unbound | Unbound | Unbound | Unbound | Unbound | Unbound | Unbound | Unbound | |||||
3il4A02 | Unbound | Unbound | Unbound | Unbound | Unbound | Unbound | Unbound | Unbound | Unbound | |||||
3il4B02 | Unbound | Unbound | Unbound | Unbound | Unbound | Unbound | Unbound | Unbound | Unbound | |||||
3il4C02 | Unbound | Unbound | Unbound | Unbound | Unbound | Unbound | Unbound | Unbound | Unbound | |||||
3il4D02 | Unbound | Unbound | Unbound | Unbound | Unbound | Unbound | Unbound | Unbound | Unbound | |||||
3il5A02 | Unbound | Unbound | Unbound | Unbound | Unbound | Unbound | Unbound | Unbound | Unbound | |||||
3il5B02 | Unbound | Unbound | Unbound | Unbound | Unbound | Unbound | Unbound | Unbound | Unbound | |||||
3il5C02 | Unbound | Unbound | Unbound | Unbound | Unbound | Unbound | Unbound | Unbound | Unbound | |||||
3il5D02 | Unbound | Unbound | Unbound | Unbound | Unbound | Unbound | Unbound | Unbound | Unbound | |||||
3il6A02 | Unbound | Unbound | Unbound | Unbound | Unbound | Unbound | Unbound | Unbound | Unbound |
Reference for Active-site residues | ||
---|---|---|
resource | references | E.C. |
literature [2], [3], [5], [9], [10], [13], [14], [15], [18], [21] & Swiss-prot;O67185, P0A6R0, P43711, Q6GIA4, Q820T1, Q8NXE2 |
Active-site residues | ||||||||||
---|---|---|---|---|---|---|---|---|---|---|
PDB | Catalytic residues | Cofactor-binding residues | Modified residues | Main-chain involved in catalysis | Comment | |||||
2ebdA01 | CYS 111;GLU 139 | CYS 111 | ||||||||
2ebdB01 | CYS 111;GLU 139 | CYS 111 | ||||||||
3il4A01 | CYS 117;GLU 145 | CYS 117 | ||||||||
3il4B01 | CYS 117;GLU 145 | CYS 117 | ||||||||
3il4C01 | CYS 117;GLU 145 | CYS 117 | ||||||||
3il4D01 | CYS 117;GLU 145 | CYS 117 | ||||||||
3il5A01 | CYS 117;GLU 145 | CYS 117 | ||||||||
3il5B01 | CYS 117;GLU 145 | CYS 117 | ||||||||
3il5C01 | CYS 117;GLU 145 | CYS 117 | ||||||||
3il5D01 | CYS 117;GLU 145 | CYS 117 | ||||||||
3il6A01 | ;GLU 145 | SCY 117(S-acetyl-cysteine) | SCY 117 | |||||||
2ebdA02 | HIS 236;ASN 266;SER 268 | GLY 298 | ||||||||
2ebdB02 | HIS 236;ASN 266;SER 268 | GLY 298 | ||||||||
3il4A02 | HIS 250;ASN 280;SER 282 | GLY 314 | mutant A192T, N253S, invisible 211-212 | |||||||
3il4B02 | HIS 250;ASN 280;SER 282 | GLY 314 | mutant A192T, N253S, invisible 211-212 | |||||||
3il4C02 | HIS 250;ASN 280;SER 282 | GLY 314 | mutant A192T, N253S, invisible 211-212 | |||||||
3il4D02 | HIS 250;ASN 280;SER 282 | GLY 314 | mutant A192T, N253S, invisible 211-212 | |||||||
3il5A02 | HIS 250;ASN 280;SER 282 | GLY 314 | ||||||||
3il5B02 | HIS 250;ASN 280;SER 282 | GLY 314 | ||||||||
3il5C02 | HIS 250;ASN 280;SER 282 | GLY 314 | ||||||||
3il5D02 | HIS 250;ASN 280;SER 282 | GLY 314 | ||||||||
3il6A02 | HIS 250;ASN 280;SER 282 | GLY 314 |
References for Catalytic Mechanism | ||
---|---|---|
References | Sections | No. of steps in catalysis |
[2]
|
Fig.6A, p.36467-36470 | |
[3]
|
Scheme 1, p.158-160 | |
[5]
|
Fig.7b, 3p.190-192 | |
[9]
|
p.349-352 | |
[10]
|
p.1561-1565 | |
[13]
|
Fig.6b, p.806-809 | |
[14]
|
Fig.6, p.32544-32547 | |
[15]
|
Fig.1 | |
[18]
|
Fig.1B | |
[21]
|
Fig.5, p.696-697 |
References | |
---|---|
[1] | |
Resource | |
Comments | X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS). |
Medline ID | |
PubMed ID | 10571059 |
Journal | FEBS Lett |
Year | 1999 |
Volume | 460 |
Pages | 46-52 |
Authors | Olsen JG, Kadziola A, von Wettstein-Knowles P, Siggaard-Andersen M, Lindquist Y, Larsen S |
Title | The X-ray crystal structure of beta-ketoacyl [acyl carrier protein] synthase I. |
Related PDB | 1dd8 |
Related UniProtKB | P0A953 |
[2] | |
Resource | |
Comments | X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS). |
Medline ID | |
PubMed ID | 10593943 |
Journal | J Biol Chem |
Year | 1999 |
Volume | 274 |
Pages | 36465-71 |
Authors | Qiu X, Janson CA, Konstantinidis AK, Nwagwu S, Silverman C, Smith WW, Khandekar S, Lonsdale J, Abdel-Meguid SS |
Title |
Crystal structure of beta-ketoacyl-acyl carrier protein synthase III. |
Related PDB | 1d9b 1hn9 |
Related UniProtKB | P0A6R0 |
[3] | |
Resource | |
Comments | |
Medline ID | |
PubMed ID | 10600651 |
Journal | Biochem J |
Year | 2000 |
Volume | 345 Pt 1 |
Pages | 153-60 |
Authors | Abbadi A, Brummel M, Schutt BS, Slabaugh MB, Schuch R, Spener F |
Title |
Reaction mechanism of recombinant 3-oxoacyl-(acyl-carrier-protein) synthase III from Cuphea wrightii embryo, |
Related PDB | |
Related UniProtKB | |
[4] | |
Resource | |
Comments | |
Medline ID | |
PubMed ID | 11006298 |
Journal | J Biol Chem |
Year | 2000 |
Volume | 275 |
Pages | 39640-6 |
Authors | Jez JM, Noel JP |
Title |
Mechanism of chalcone synthase. |
Related PDB | |
Related UniProtKB | |
[5] | |
Resource | |
Comments | X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS). |
Medline ID | |
PubMed ID | 10673437 |
Journal | Structure |
Year | 2000 |
Volume | 8 |
Pages | 185-95 |
Authors | Davies C, Heath RJ, White SW, Rock CO |
Title | The 1.8 A crystal structure and active-site architecture of beta-ketoacyl-acyl carrier protein synthase III (FabH) from escherichia coli. |
Related PDB | 1ebl |
Related UniProtKB | P0A6R0 |
[6] | |
Resource | |
Comments | |
Medline ID | |
PubMed ID | 11502177 |
Journal | Biochemistry |
Year | 2001 |
Volume | 40 |
Pages | 9836-45 |
Authors | McGuire KA, Siggaard-Andersen M, Bangera MG, Olsen JG, von Wettstein-Knowles P |
Title | beta-Ketoacyl-[acyl carrier protein] synthase I of Escherichia coli: aspects of the condensation mechanism revealed by analyses of mutations in the active site pocket. |
Related PDB | |
Related UniProtKB | |
[7] | |
Resource | |
Comments | X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS). |
Medline ID | |
PubMed ID | 11278743 |
Journal | J Biol Chem |
Year | 2001 |
Volume | 276 |
Pages | 20516-22 |
Authors | Scarsdale JN, Kazanina G, He X, Reynolds KA, Wright HT |
Title | Crystal structure of the Mycobacterium tuberculosis beta-ketoacyl-acyl carrier protein synthase III. |
Related PDB | 1hzp |
Related UniProtKB | P0A574 |
[8] | |
Resource | |
Comments | |
Medline ID | |
PubMed ID | 11078736 |
Journal | J Biol Chem |
Year | 2001 |
Volume | 276 |
Pages | 8231-8 |
Authors | Zhang YM, Rao MS, Heath RJ, Price AC, Olson AJ, Rock CO, White SW |
Title | Identification and analysis of the acyl carrier protein (ACP) docking site on beta-ketoacyl-ACP synthase III. |
Related PDB | |
Related UniProtKB | |
[9] | |
Resource | |
Comments | X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS). |
Medline ID | |
PubMed ID | 11243824 |
Journal | J Mol Biol |
Year | 2001 |
Volume | 307 |
Pages | 341-56 |
Authors | Qiu X, Janson CA, Smith WW, Head M, Lonsdale J, Konstantinidis AK |
Title | Refined structures of beta-ketoacyl-acyl carrier protein synthase III. |
Related PDB | 1hnd 1hnh 1hnj 1hnk |
Related UniProtKB | P0A6R0 |
[10] | |
Resource | |
Comments | X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS). |
Medline ID | |
PubMed ID | 12429097 |
Journal | Structure |
Year | 2002 |
Volume | 10 |
Pages | 1559-68 |
Authors | Pan H, Tsai S, Meadows ES, Miercke LJ, Keatinge-Clay AT, O'Connell J, Khosla C, Stroud RM |
Title | Crystal structure of the priming beta-ketosynthase from the R1128 polyketide biosynthetic pathway. |
Related PDB | 1mzj |
Related UniProtKB | Q9F6D4 |
[11] | |
Resource | |
Comments | |
Medline ID | |
PubMed ID | 12502353 |
Journal | J Med Chem |
Year | 2003 |
Volume | 46 |
Pages | 5-8 |
Authors | Daines RA, Pendrak I, Sham K, Van Aller GS, Konstantinidis AK, Lonsdale JT, Janson CA, Qiu X, Brandt M, Khandekar SS, Silverman C, Head MS |
Title | First X-ray cocrystal structure of a bacterial FabH condensing enzyme and a small molecule inhibitor achieved using rational design and homology modeling. |
Related PDB | 1mzs |
Related UniProtKB | |
[12] | |
Resource | |
Comments | |
Medline ID | |
PubMed ID | 12866053 |
Journal | Proteins |
Year | 2003 |
Volume | 52 |
Pages | 427-35 |
Authors | Dawe JH, Porter CT, Thornton JM, Tabor AB |
Title | A template search reveals mechanistic similarities and differences in beta-ketoacyl synthases (KAS) and related enzymes. |
Related PDB | |
Related UniProtKB | |
[13] | |
Resource | |
Comments | |
Medline ID | |
PubMed ID | 15952903 |
Journal | Annu Rev Biochem |
Year | 2005 |
Volume | 74 |
Pages | 791-831 |
Authors | White SW, Zheng J, Zhang YM, Rock |
Title | The structural biology of type II fatty acid biosynthesis. |
Related PDB | |
Related UniProtKB | |
[14] | |
Resource | |
Comments | |
Medline ID | |
PubMed ID | 16040614 |
Journal | J Biol Chem |
Year | 2005 |
Volume | 280 |
Pages | 32539-47 |
Authors | Brown AK, Sridharan S, Kremer L, Lindenberg S, Dover LG, Sacchettini JC, Besra GS |
Title | Probing the mechanism of the Mycobacterium tuberculosis beta-ketoacyl-acyl carrier protein synthase III mtFabH: factors influencing catalysis and substrate specificity. |
Related PDB | 1m1m 2ahb 2aj9 |
Related UniProtKB | |
[15] | |
Resource | |
Comments | |
Medline ID | |
PubMed ID | 15713483 |
Journal | J Mol Biol |
Year | 2005 |
Volume | 346 |
Pages | 1313-21 |
Authors | Musayev F, Sachdeva S, Scarsdale JN, Reynolds KA, Wright HT |
Title | Crystal structure of a substrate complex of Mycobacterium tuberculosis beta-ketoacyl-acyl carrier protein synthase III (FabH) with lauroyl-coenzyme A. |
Related PDB | 1u6e 1u6s |
Related UniProtKB | |
[16] | |
Resource | |
Comments | |
Medline ID | |
PubMed ID | 15987898 |
Journal | Protein Sci |
Year | 2005 |
Volume | 14 |
Pages | 2087-94 |
Authors | Qiu X, Choudhry AE, Janson CA, Grooms M, Daines RA, Lonsdale JT, Khandekar SS |
Title | Crystal structure and substrate specificity of the beta-ketoacyl-acyl carrier protein synthase III (FabH) from Staphylococcus aureus. |
Related PDB | 1zow |
Related UniProtKB | |
[17] | |
Resource | |
Comments | |
Medline ID | |
PubMed ID | 16356722 |
Journal | Trends Biochem Sci |
Year | 2005 |
Volume | 31 |
Pages | 64-71 |
Authors | Haapalainen AM, Merilainen G, Wierenga RK |
Title | The thiolase superfamily: condensing enzymes with diverse reaction specificities. |
Related PDB | |
Related UniProtKB | |
[18] | |
Resource | |
Comments | |
Medline ID | |
PubMed ID | 17524982 |
Journal | Chem Biol |
Year | 2007 |
Volume | 14 |
Pages | 513-24 |
Authors | Alhamadsheh MM, Musayev F, Komissarov AA, Sachdeva S, Wright HT, Scarsdale N, Florova G, Reynolds KA |
Title | Alkyl-CoA disulfides as inhibitors and mechanistic probes for FabH enzymes. |
Related PDB | 2eft 2gyo |
Related UniProtKB | |
[19] | |
Resource | |
Comments | |
Medline ID | |
PubMed ID | 18096200 |
Journal | Bioorg Chem |
Year | 2008 |
Volume | 36 |
Pages | 85-90 |
Authors | Sachdeva S, Musayev F, Alhamadsheh MM, Neel Scarsdale J, Tonie Wright H, Reynolds KA |
Title | Probing reactivity and substrate specificity of both subunits of the dimeric Mycobacterium tuberculosis FabH using alkyl-CoA disulfide inhibitors and acyl-CoA substrates. |
Related PDB | |
Related UniProtKB | |
[20] | |
Resource | |
Comments | |
Medline ID | |
PubMed ID | 18420147 |
Journal | Chem Biol |
Year | 2008 |
Volume | 15 |
Pages | 402-12 |
Authors | Sachdeva S, Musayev FN, Alhamadsheh MM, Scarsdale JN, Wright HT, Reynolds KA |
Title | Separate entrance and exit portals for ligand traffic in Mycobacterium tuberculosis FabH. |
Related PDB | 2qnz 2qny 2qnx 2qo0 2qo1 |
Related UniProtKB | |
[21] | |
Resource | |
Comments | |
Medline ID | |
PubMed ID | 18824113 |
Journal | Mol Phylogenet Evol |
Year | 2008 |
Volume | 49 |
Pages | 691-701 |
Authors | Jiang C, Kim SY, Suh DY |
Title | Divergent evolution of the thiolase superfamily and chalcone synthase family. |
Related PDB | |
Related UniProtKB | |
[22] | |
Resource | |
Comments | |
Medline ID | |
PubMed ID | 19665020 |
Journal | FEBS Lett |
Year | 2009 |
Volume | 583 |
Pages | 2939-46 |
Authors | Gajiwala KS, Margosiak S, Lu J, Cortez J, Su Y, Nie Z, Appelt K |
Title | Crystal structures of bacterial FabH suggest a molecular basis for the substrate specificity of the enzyme. |
Related PDB | 3il3 3il4 3il5 3il6 3il7 3il9 |
Related UniProtKB |
Comments |
---|
This enzyme belongs to chalcone synthase family in thiolase superfamily (see [21]). According to the literature, According to the literature [2], (A) Transfer of acyl group from sulfur atom of acetyl-CoA to catalytic cysteine (see [9]): (A0) Asn266 (of 2ebd) modulate the pKa of His236, (A1) Glu139 acts as a general base to deprotonate the nucleophile, (A2) The activated thiol group of Cys111 makes a nucleophilic attack on the acetyl group of acetyl-CoA, (A3) His236 acts as a general acid to protonate the leaving sulfur atom of CoA, (B) Decarboxylation of malonyl-ACP (Elimination of carboxylate group from malonyl group) forming carbanion/enolate transition-state (I00134): (B0) Asn266 and His236 interact with the carbonyl oxygen of the second substrate, (B1) His236 may act as a general base to deprotonate the carboxylic group of malonyl-ACP, (C) Transfer of acetyl group from catalytic cysteine to carbanion on the transition-state (I00134): (C0) Asn266 and His236 stabilize the enol group of the transition-state (I00134). (C1) The carbanion makes a nucleophilic attack on the acetyl group of the acetyl intermediate (I00133), (C2) Glu139 may act as a general acid to protonate the leaving catalytic residue, |
Created | Updated |
---|---|
2009-11-26 | 2012-07-06 |