DB code: D00825

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 D00826 D00867 D00871

Uniprot Enzyme Name
UniprotKB Protein name Synonyms RefSeq Pfam
P0A6R0 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
EcFabH
NP_415609.1 (Protein)
NC_000913.2 (DNA/RNA sequence)
YP_489359.1 (Protein)
NC_007779.1 (DNA/RNA sequence)
PF08545 (ACP_syn_III)
PF08541 (ACP_syn_III_C)
[Graphical View]
P43711 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_438327.1 (Protein)
NC_000907.1 (DNA/RNA sequence)
PF08545 (ACP_syn_III)
PF08541 (ACP_syn_III_C)
[Graphical View]
Q6GIA4 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
YP_040368.1 (Protein)
NC_002952.2 (DNA/RNA sequence)
PF08545 (ACP_syn_III)
PF08541 (ACP_syn_III_C)
[Graphical View]
Q8NXE2 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_645682.1 (Protein)
NC_003923.1 (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
P0A6R0 FABH_ECOLI Acetyl-CoA + malonyl-[acyl-carrier-protein] = acetoacyl-[acyl-carrier-protein] + CoA + CO2. Homodimer. Cytoplasm.
P43711 FABH_HAEIN Acetyl-CoA + malonyl-[acyl-carrier-protein] = acetoacyl-[acyl-carrier-protein] + CoA + CO2. Homodimer (By similarity). Cytoplasm (Probable).
Q6GIA4 FABH_STAAR Acetyl-CoA + malonyl-[acyl-carrier-protein] = acetoacyl-[acyl-carrier-protein] + CoA + CO2. Homodimer (By similarity). Cytoplasm (Probable).
Q8NXE2 FABH_STAAW 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
1d9bA01 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1d9bB01 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1eblA01 Unbound Unbound Unbound Bound:COA Unbound Unbound Unbound Unbound Unbound
1eblB01 Unbound Unbound Unbound Bound:COA Unbound Unbound Unbound Unbound Unbound
1hn9A01 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1hn9B01 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1hndA01 Unbound Unbound Unbound Bound:COA Unbound Unbound Unbound Unbound Unbound
1hnhA01 Unbound Unbound Unbound Bound:COA Unbound Unbound Intermediate-bound:SCY Unbound Unbound
1hnjA01 Unbound Unbound Unbound Bound:MLC Unbound Unbound Unbound Unbound Unbound
1hnkA01 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1mzsA01 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
2eftA01 Unbound Unbound Unbound Bound:COA Unbound Unbound Intermediate-analogue:MEE-CYS_112 Unbound Unbound
2eftB01 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
2gyoA01 Unbound Unbound Unbound Bound:COA Unbound Unbound Intermediate-analogue:MEE-CYS_112 Unbound Unbound
2gyoB01 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
3il9A01 Unbound Unbound Unbound Unbound Unbound Unbound Intermediate-analogue:CSW Unbound Unbound
3il9B01 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
3il3A01 Unbound Unbound Unbound Unbound Unbound Unbound Intermediate-bound:SCY Unbound Unbound
3il7A01 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
3il7B01 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1zowA01 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1zowB01 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1zowC01 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1zowD01 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1d9bA02 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1d9bB02 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1eblA02 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1eblB02 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1hn9A02 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1hn9B02 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1hndA02 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1hnhA02 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1hnjA02 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1hnkA02 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1mzsA02 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
2eftA02 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
2eftB02 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
2gyoA02 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
2gyoB02 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
3il9A02 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
3il9B02 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
3il3A02 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
3il7A02 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
3il7B02 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1zowA02 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1zowB02 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1zowC02 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1zowD02 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
1d9bA01 CYS 112;ASP 140 CYS 112
1d9bB01 CYS 112;ASP 140 CYS 112
1eblA01 CYS 112;ASP 140 CYS 112
1eblB01 CYS 112;ASP 140 CYS 112
1hn9A01 CYS 112;ASP 140 CYS 112
1hn9B01 CYS 1112;ASP 1140 CYS 1112
1hndA01 CYS 112;ASP 140 CYS 112
1hnhA01 ;ASP 140 SCY 112(S-acetyl-cysteine) SCY 112
1hnjA01 CYS 112;ASP 140 CYS 112
1hnkA01 CYS 112;ASP 140 CYS 112 invisible 84-86, 146-152
1mzsA01 ;ASP 140 OCS 112(sulfinocysteine) OCS 112
2eftA01 CYS 112;ASP 140 CYS 112
2eftB01 CYS 112;ASP 140 CYS 112
2gyoA01 CYS 112;ASP 140 CYS 112
2gyoB01 CYS 112;ASP 140 CYS 112
3il9A01 ;ASP 140 CSW 112(cystein-S-dioxide) CSW 112
3il9B01 ;ASP 140 CSW 112(cystein-S-dioxide) CSW 112
3il3A01 ;ASP 140 SCY 112(S-acetyl-cysteine) SCY 112
3il7A01 CYS 112;ASP 140 CYS 112
3il7B01 CYS 112;ASP 140 CYS 112
1zowA01 CYS 112;ASP 140 CYS 112
1zowB01 CYS 112;ASP 140 CYS 112
1zowC01 CYS 112;ASP 140 CYS 112
1zowD01 CYS 112;ASP 140 CYS 112
1d9bA02 HIS 244;ASN 274;SER 276 GLY 306
1d9bB02 HIS 244;ASN 274;SER 276 GLY 306
1eblA02 HIS 244;ASN 274;SER 276 GLY 306
1eblB02 HIS 244;ASN 274;SER 276 GLY 306
1hn9A02 HIS 244;ASN 274;SER 276 GLY 306
1hn9B02 HIS 1244;ASN 1274;SER 1276 GLY 1306
1hndA02 HIS 244;ASN 274;SER 276 GLY 306
1hnhA02 HIS 244;ASN 274;SER 276 GLY 306
1hnjA02 HIS 244;ASN 274;SER 276 GLY 306
1hnkA02 HIS 244;ASN 274;SER 276 invisible 185-217, 305-307
1mzsA02 HIS 244;ASN 274;SER 276 GLY 306
2eftA02 HIS 244;ASN 274;SER 276 GLY 306
2eftB02 HIS 244;ASN 274;SER 276 GLY 306
2gyoA02 HIS 244;ASN 274;SER 276 GLY 306
2gyoB02 HIS 244;ASN 274;SER 276 GLY 306
3il9A02 HIS 244;ASN 274;SER 276 GLY 306
3il9B02 HIS 244;ASN 274;SER 276 GLY 306
3il3A02 HIS 243;ASN 273;SER 275 GLY 305
3il7A02 HIS 238;ASN 268;SER 270 GLY 300
3il7B02 HIS 238;ASN 268;SER 270 GLY 300
1zowA02 HIS 238;ASN 268;SER 270 GLY 300
1zowB02 HIS 238;ASN 268;SER 270 GLY 300
1zowC02 HIS 238;ASN 268;SER 270 GLY 300
1zowD02 HIS 238;ASN 268;SER 270 GLY 300

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. A key condensing enzyme in bacterial fatty acid biosynthesis.
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, a fatty acid synthase type II condensing enzyme.
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. pKa of the catalytic cysteine and the role of the conserved histidine in a plant polyketide 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]). This enzyme is homologous to the counterpart enzymes from different bacteria (D00826 and D00867 in EzCatDB), with a slightly different catalytic site. Moreover, these enzymes are categorized in type III of beta-ketoacyl-acyl-carrier protein synthases (KAS).
According to the literature, the catalysis proceeds through the Ping-Pong reaction mechanism.
According to the literature [2], [3], [5], [9], [10], [14], [15] and [21], this enzyme catalyzes the following reactions:
(A) Transfer of acyl group from sulfur atom of acetyl-CoA to catalytic cysteine (see [9]):
(A0) Asn274 (of 1d9b) modulate the pKa of His244, whereas His244 may lower the pKa of the sidechain of Cys112.
(A1) Asp140 acts as a general base to deprotonate the nucleophile, Cys112, through the sidechain of Ser276. (Helix dipole moment may also activate the cysteine sidechain.)
(A2) The activated thiol group of Cys112 makes a nucleophilic attack on the acetyl group of acetyl-CoA, leading to a transition-state (I00132). The oxyanion hole, composed of the mainchain amide groups of Cys112 and Gly306, stabilizes the negative charge of the oxyanion on the tetrahedral transition-state (I00132).
(A3) His244 acts as a general acid to protonate the leaving sulfur atom of CoA, generating an acetyl group on Cys112 (I00133).
(B) Decarboxylation of malonyl-ACP (Elimination of carboxylate group from malonyl group) forming carbanion/enolate transition-state (I00134):
(B0) Asn274 and His244 interact with the carbonyl oxygen of the second substrate, malonyl-ACP, and stabilize it.
(B1) His244 may act as a general base to deprotonate the carboxylic group of malonyl-ACP, to facilitate the decarboxylation. This reaction generates a carbanion/enolate transition-state (I00134). The enolate is stabilized by Asn274 and His244.
(C) Transfer of acetyl group from catalytic cysteine to carbanion on the transition-state (I00134):
(C0) Asn274 and His244 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), forming a tetrahedral transition-state (I00135). The oxyanion of the tetrahedral transition-state (I00135) is stabilized by the oxyanion hole composed of the mainchain amide groups of Cys112 and Gly306.
(C2) Asp140 may act as a general acid to protonate the leaving catalytic residue, Cys112, through the sidechain of Ser276.

Created Updated
2009-11-26 2012-07-10