EzCatDB: D00871

DB codeD00871
RLCP classification3.1177.220085.58
1.51.790.101
3.1197.15025.150
CATH domainDomain 13.40.47.10Catalytic domain
Domain 23.40.47.10Catalytic domain
E.C.2.3.1.179
CSA1kas

CATH domainRelated DB codes (homologues)
3.40.47.10D00090,D00411,D00509,D00825,D00826,D00867

Enzyme Name
Swiss-protKEGG

P0AAI5Q6G441Q8YFP7A4JL30P73283Q5SL80Q8NXE1Q8Y574Q9FBC2
Protein name3-oxoacyl-[acyl-carrier-protein] synthase 2


3-oxoacyl-[acyl-carrier-protein] synthase 2
3-oxoacyl-[acyl-carrier-protein] synthase 2
(Beta-ketoacyl-ACP synthase IIbeta-ketoacyl-acyl-carrier-protein synthase II
KASII
KAS II
FabF
3-oxoacyl-acyl carrier protein synthase I
beta-ketoacyl-ACP synthase II
(Z)-hexadec-11-enoyl-[acyl-carrier-protein]:malonyl-[acyl-carrier-protein] C-acyltransferase (decarboxylating)
SynonymsEC 2.3.1.179
3-oxoacyl-[acyl-carrier-protein] synthase II
Beta-ketoacyl-ACP synthase II
KAS II
3-oxoacyl-[acyl-carrier-protein ] synthase II
3-OXOACYL-(ACYL-CARRIER-PROTEIN) SYNTHASE II
EC 2.3.1.41
3-oxoacyl-[acyl-carrier-protein] synthase II
EC 2.3.1.41
EC 2.3.1.179
3-oxoacyl-[acyl-carrier-protein] synthase II
Beta-ketoacyl-ACP synthase II
KAS II
3-oxoacyl-[acyl carrier protein] synthase II
EC 2.3.1.179
3-oxoacyl-[acyl-carrier-protein] synthase II
Beta-ketoacyl-ACP synthase II
KAS II
Lmo2201 protein
3-oxoacyl-(Acyl-carrier-protein) synthase II)
EC 2.3.1.41

KEGG pathways
MAP codePathways
MAP00061Fatty acid biosynthesis

Swiss-prot:Accession NumberP0AAI5Q6G441Q8YFP7A4JL30P73283Q5SL80Q8NXE1Q8Y574Q9FBC2
Entry nameFABF_ECOLIQ6G441_BARHEQ8YFP7_BRUMEA4JL30_BURVGFABF_SYNY3Q5SL80_THET8FABF_STAAWQ8Y574_LISMOQ9FBC2_STRPN
Activity(Z)-hexadec-11-enoyl-[acyl-carrier-protein] + malonyl-[acyl-carrier-protein] = (Z)-3-oxooctadec-13-enoyl-[acyl-carrier-protein] + CO2 + [acyl-carrier-protein].
(Z)-hexadec-11-enoyl-[acyl-carrier-protein] + malonyl-[acyl-carrier-protein] = (Z)-3-oxooctadec-13-enoyl-[acyl-carrier-protein] + CO(2) + [acyl-carrier-protein].(Z)-hexadec-11-enoyl-[acyl-carrier-protein] + malonyl-[acyl-carrier-protein] = (Z)-3-oxooctadec-13-enoyl-[acyl-carrier-protein] + CO(2) + [acyl-carrier-protein].(Z)-hexadec-11-enoyl-[acyl-carrier-protein] + malonyl-[acyl-carrier-protein] = (Z)-3-oxooctadec-13-enoyl-[acyl-carrier-protein] + CO2 + [acyl-carrier-protein].
(Z)-hexadec-11-enoyl-[acyl-carrier-protein] + malonyl-[acyl-carrier-protein] = (Z)-3-oxooctadec-13-enoyl-[acyl-carrier-protein] + CO2 + [acyl-carrier-protein].(Z)-hexadec-11-enoyl-[acyl-carrier-protein] + malonyl-[acyl-carrier-protein] = (Z)-3-oxooctadec-13-enoyl-[acyl-carrier-protein] + CO(2) + [acyl-carrier-protein].
SubunitHomodimer.


Homodimer.



Subcellular location








Cofactor










SubstratesProductsintermediates
KEGG-idC01209L00039C00001C00288C00229L00040I00138I00139I00140I00134I00141
Compoundmalonyl-[acyl-carrier-protein](Z)-hexadec-11-enoyl-[acyl-carrier protein]H2OBicabonate(HCO3-)[acyl-carrier-protein](Z)-3-oxooctadec-13-enoyl-[acyl-carrier protein]Peptidyl-Cys-tetrahedral-(Z)-hexadec-11-enoyl-[acyl-carrier protein]Peptidyl-Cys-S-(Z)-hexadec-11-enoyl[Acyl-carrier protein]-tetrahedral-malonyl group[Acyl-carrier protein]-decarboxylated malonyl group (Peptidyl-Ser-phosphopantetheine-S-enolate)Peptidyl-Cys-tetrahedral-(Z)-hexadec-11-enoyl-keto-[acyl-carrier protein]
Typecarbohydrate,carboxyl group,peptide/protein,phosphate group/phosphate ion,sulfide groupcarbohydrate,lipid,peptide/protein,phosphate group/phosphate ion,sulfide groupH2Ocarboxyl groupcarbohydrate,peptide/protein,phosphate group/phosphate ion,sulfhydryl groupcarbohydrate,lipid,peptide/protein,phosphate group/phosphate ion,sulfide group




1b3nA01UnboundUnbound
UnboundUnboundUnboundUnboundUnboundUnboundUnboundTransition-state-analogue:CER
1kas001UnboundUnbound
UnboundUnboundUnboundUnboundUnboundUnboundUnboundUnbound
2gfvA01UnboundUnbound
UnboundUnboundUnboundUnboundUnboundUnboundUnboundUnbound
2gfwA01UnboundUnbound
UnboundUnboundUnboundUnboundUnboundUnboundUnboundUnbound
2gfxA01UnboundUnbound
UnboundUnboundUnboundUnboundUnboundUnboundUnboundUnbound
2gfyA01UnboundUnbound
UnboundUnboundUnboundUnboundIntermediate-analogue:DAOUnboundUnboundUnbound
3g0yA01UnboundUnbound
UnboundUnboundUnboundUnboundUnboundUnboundUnboundUnbound
3g11A01UnboundUnbound
UnboundUnboundUnboundUnboundUnboundUnboundUnboundUnbound
3hnzA01UnboundUnbound
UnboundUnboundUnboundUnboundUnboundUnboundUnboundUnbound
3ho2A01UnboundUnbound
UnboundUnboundUnboundUnboundUnboundUnboundUnboundUnbound
3ho9A01UnboundUnbound
UnboundUnboundUnboundUnboundUnboundUnboundUnboundUnbound
3i8pA01UnboundUnbound
UnboundUnboundUnboundUnboundUnboundUnboundUnboundUnbound
3e60A01UnboundUnbound
UnboundUnboundUnboundUnboundUnboundUnboundUnboundUnbound
3e60B01UnboundUnbound
UnboundUnboundUnboundUnboundUnboundUnboundUnboundUnbound
3kzuA01UnboundUnbound
UnboundUnboundUnboundUnboundUnboundUnboundUnboundUnbound
3kzuB01UnboundUnbound
UnboundUnboundUnboundUnboundUnboundUnboundUnboundUnbound
3kzuC01UnboundUnbound
UnboundUnboundUnboundUnboundUnboundUnboundUnboundUnbound
4ddoA01UnboundUnbound
UnboundUnboundUnboundUnboundUnboundUnboundUnboundUnbound
4f32A01UnboundUnbound
UnboundUnboundUnboundUnboundUnboundUnboundUnboundUnbound
4f32B01UnboundUnbound
UnboundUnboundUnboundUnboundUnboundUnboundUnboundUnbound
1e5mA01UnboundUnbound
UnboundUnboundUnboundUnboundUnboundUnboundUnboundUnbound
1j3nA01UnboundUnbound
UnboundUnboundUnboundUnboundUnboundUnboundUnboundUnbound
1j3nB01UnboundUnbound
UnboundUnboundUnboundUnboundUnboundUnboundUnboundUnbound
2gqdA01UnboundUnbound
UnboundUnboundUnboundUnboundUnboundUnboundUnboundUnbound
2gqdB01UnboundUnbound
UnboundUnboundUnboundUnboundUnboundUnboundUnboundUnbound
3o04A01UnboundUnbound
UnboundUnboundUnboundUnboundUnboundUnboundUnboundUnbound
1ox0A01UnboundUnbound
UnboundUnboundUnboundUnboundUnboundUnboundUnboundUnbound
1oxhA01UnboundUnbound
UnboundUnboundUnboundUnboundUnboundUnboundUnboundUnbound
1oxhB01UnboundUnbound
UnboundUnboundUnboundUnboundUnboundUnboundUnboundUnbound
1oxhC01UnboundUnbound
UnboundUnboundUnboundUnboundUnboundUnboundUnboundUnbound
1oxhD01UnboundUnbound
UnboundUnboundUnboundUnboundUnboundUnboundUnboundUnbound
2almA01UnboundUnbound
UnboundUnboundUnboundUnboundUnboundUnboundUnboundUnbound
2rjtA01UnboundUnbound
UnboundUnboundUnboundUnboundUnboundUnboundUnboundUnbound
2rjtB01UnboundUnbound
UnboundUnboundUnboundUnboundUnboundUnboundUnboundUnbound
2rjtC01UnboundUnbound
UnboundUnboundUnboundUnboundUnboundUnboundUnboundUnbound
2rjtD01UnboundUnbound
UnboundUnboundUnboundUnboundUnboundUnboundUnboundUnbound
1b3nA02UnboundUnbound
UnboundUnboundUnboundUnboundUnboundUnboundUnboundUnbound
1kas002UnboundUnbound
UnboundUnboundUnboundUnboundUnboundUnboundUnboundUnbound
2gfvA02UnboundUnbound
UnboundUnboundUnboundUnboundUnboundUnboundUnboundUnbound
2gfwA02UnboundUnbound
UnboundUnboundUnboundUnboundUnboundUnboundUnboundUnbound
2gfxA02Analogue:PMNUnbound
UnboundUnboundUnboundUnboundUnboundUnboundUnboundUnbound
2gfyA02UnboundUnbound
UnboundUnboundUnboundUnboundUnboundUnboundUnboundUnbound
3g0yA02Analogue:P9AUnbound
UnboundUnboundUnboundUnboundUnboundUnboundUnboundUnbound
3g11A02Analogue:P9CUnbound
UnboundUnboundUnboundUnboundUnboundUnboundUnboundUnbound
3hnzA02Analogue:PMNUnbound
UnboundUnboundUnboundUnboundUnboundUnboundUnboundUnbound
3ho2A02Analogue:N32Unbound
UnboundUnboundUnboundUnboundUnboundUnboundUnboundUnbound
3ho9A02Analogue:N3AUnbound
UnboundUnboundUnboundUnboundUnboundUnboundUnboundUnbound
3i8pA02Analogue:840Unbound
UnboundUnboundUnboundUnboundUnboundUnboundUnboundUnbound
3e60A02UnboundUnbound
UnboundUnboundUnboundUnboundUnboundUnboundUnboundUnbound
3e60B02UnboundUnbound
UnboundUnboundUnboundUnboundUnboundUnboundUnboundUnbound
3kzuA02UnboundUnbound
UnboundUnboundUnboundUnboundUnboundUnboundUnboundUnbound
3kzuB02UnboundUnbound
UnboundUnboundUnboundUnboundUnboundUnboundUnboundUnbound
3kzuC02UnboundUnbound
UnboundUnboundUnboundUnboundUnboundUnboundUnboundUnbound
4ddoA02UnboundUnbound
UnboundUnboundUnboundUnboundUnboundUnboundUnboundUnbound
4f32A02Analogue:N32Unbound
UnboundUnboundUnboundUnboundUnboundUnboundUnboundUnbound
4f32B02Analogue:N32Unbound
UnboundUnboundUnboundUnboundUnboundUnboundUnboundUnbound
1e5mA02UnboundUnbound
UnboundUnboundUnboundUnboundUnboundUnboundUnboundUnbound
1j3nA02UnboundUnbound
UnboundUnboundUnboundUnboundUnboundUnboundUnboundUnbound
1j3nB02UnboundUnbound
UnboundUnboundUnboundUnboundUnboundUnboundUnboundUnbound
2gqdA02UnboundUnbound
UnboundUnboundUnboundUnboundUnboundUnboundUnboundUnbound
2gqdB02UnboundUnbound
UnboundUnboundUnboundUnboundUnboundUnboundUnboundUnbound
3o04A02UnboundUnbound
UnboundUnboundUnboundUnboundUnboundUnboundUnboundUnbound
1ox0A02UnboundUnbound
UnboundUnboundUnboundUnboundUnboundUnboundUnboundUnbound
1oxhA02UnboundUnbound
UnboundUnboundUnboundUnboundUnboundUnboundUnboundUnbound
1oxhB02UnboundUnbound
UnboundUnboundUnboundUnboundUnboundUnboundUnboundUnbound
1oxhC02UnboundUnbound
UnboundUnboundUnboundUnboundUnboundUnboundUnboundUnbound
1oxhD02UnboundUnbound
UnboundUnboundUnboundUnboundUnboundUnboundUnboundUnbound
2almA02UnboundUnbound
UnboundUnboundUnboundUnboundUnboundUnboundUnboundUnbound
2rjtA02UnboundUnbound
UnboundUnboundUnboundUnboundUnboundUnboundUnboundUnbound
2rjtB02UnboundUnbound
UnboundUnboundUnboundUnboundUnboundUnboundUnboundUnbound
2rjtC02UnboundUnbound
UnboundUnboundUnboundUnboundUnboundUnboundUnboundUnbound
2rjtD02UnboundUnbound
UnboundUnboundUnboundUnboundUnboundUnboundUnboundUnbound

Active-site residues
resource
literature [1], [8], [10], [13], [14], [15], [16], [17], [20], [24], [30] [31] & CSA;1dd8
pdbCatalytic residuesModified residuesMain-chain involved in catalysiscomment
1b3nA01CYS 163
                                 
CYS 163

1kas001CYS 163
                                 
CYS 163

2gfvA01       
                                 
       
mutant C163Q
2gfwA01CYS 163
                                 
CYS 163

2gfxA01       
                                 
       
mutant C163Q
2gfyA01CYS 163
                                 
CYS 163

3g0yA01       
                                 
       
mutant C163Q
3g11A01       
                                 
       
mutant C163Q
3hnzA01       
                                 
       
mutant C163A
3ho2A01       
                                 
       
mutant C163A
3ho9A01       
                                 
       
mutant C163A
3i8pA01       
                                 
       
mutant C163A
3e60A01CYS 170
                                 
CYS 170

3e60B01CYS 170
                                 
CYS 170

3kzuA01CYS 170
                                 
CYS 170

3kzuB01CYS 170
                                 
CYS 170

3kzuC01CYS 170
                                 
CYS 170

4ddoA01CYS 172
                                 
CYS 172

4f32A01       
CSU 172(Cysteine-S-Sulfonic acid)
CSU 172

4f32B01       
CSU 172(Cysteine-S-Sulfonic acid)
CSU 172

1e5mA01CYS 167
                                 
CYS 167

1j3nA01CYS 161
                                 
CYS 161

1j3nB01CYS 161
                                 
CYS 161

2gqdA01CYS 165
                                 
CYS 165

2gqdB01CYS 165
                                 
CYS 165

3o04A01CYS 164
                                 
CYS 164

1ox0A01CYS 164
                                 
CYS 164

1oxhA01CYS 164
                                 
CYS 164

1oxhB01CYS 164
                                 
CYS 164

1oxhC01CYS 164
                                 
CYS 164

1oxhD01CYS 164
                                 
CYS 164

2almA01CYS 164
                                 
CYS 164

2rjtA01CYS 164
                                 
CYS 164

2rjtB01CYS 164
                                 
CYS 164

2rjtC01CYS 164
                                 
CYS 164

2rjtD01CYS 164
                                 
CYS 164

1b3nA02HIS 303;LYS 335;HIS 340

PHE 400

1kas002HIS 303;LYS 335;HIS 340

PHE 400

2gfvA02HIS 303;LYS 335;HIS 340

PHE 400

2gfwA02HIS 303;LYS 335;HIS 340

PHE 400

2gfxA02HIS 303;LYS 335;HIS 340

PHE 400

2gfyA02HIS 303;       ;HIS 340

PHE 400
mutant K335A
3g0yA02HIS 303;LYS 335;HIS 340

PHE 400

3g11A02HIS 303;LYS 335;HIS 340

PHE 400

3hnzA02HIS 303;LYS 335;HIS 340

PHE 400

3ho2A02HIS 303;LYS 335;HIS 340

PHE 400

3ho9A02HIS 303;LYS 335;HIS 340

PHE 400

3i8pA02HIS 303;LYS 335;HIS 340

PHE 400

3e60A02HIS 311;LYS 342;HIS 347

PHE 406

3e60B02HIS 311;LYS 342;HIS 347

PHE 406

3kzuA02HIS 311;LYS 342;HIS 347

PHE 406

3kzuB02HIS 311;LYS 342;HIS 347

PHE 406

3kzuC02HIS 311;LYS 342;HIS 347

PHE 406

4ddoA02HIS 313;LYS 344;HIS 349

PHE 409

4f32A02HIS 313;LYS 344;HIS 349

PHE 409

4f32B02HIS 313;LYS 344;HIS 349

PHE 409

1e5mA02HIS 307;LYS 339;HIS 344

PHE 403

1j3nA02HIS 301;LYS 333;HIS 338

PHE 396

1j3nB02HIS 301;LYS 333;HIS 338

PHE 396

2gqdA02HIS 304;LYS 336;HIS 341

PHE 400

2gqdB02HIS 304;LYS 336;HIS 341

PHE 400

3o04A02HIS 303;LYS 335;HIS 340

PHE 399

1ox0A02HIS 303;LYS 332;HIS 337

PHE 396

1oxhA02HIS 303;LYS 332;HIS 337

PHE 396

1oxhB02HIS 303;LYS 332;HIS 337

PHE 396

1oxhC02HIS 303;LYS 332;HIS 337

PHE 396

1oxhD02HIS 303;LYS 332;HIS 337

PHE 396

2almA02       ;LYS 332;HIS 337

PHE 396
mutant H303A, G379A
2rjtA02HIS 303;LYS 332;HIS 337

PHE 396
mutant E22A, E94A, E325A, E383A, E409A
2rjtB02HIS 303;LYS 332;HIS 337

PHE 396
mutant E22A, E94A, E325A, E383A, E409A
2rjtC02HIS 303;LYS 332;HIS 337

PHE 396
mutant E22A, E94A, E325A, E383A, E409A
2rjtD02HIS 303;LYS 332;HIS 337

PHE 396
mutant E22A, E94A, E325A, E383A, E409A

References for Catalytic Mechanism
ReferencesSectionsNo. of steps in catalysis
[1]p.1186-1189
[3]Fig.1B, p.603-604
[5]p.9842-9844
[6]Table 4, p.496-498
[7]Fig.6, p.10883-10887
[8]p.4139-4141
[9]Fig.8, p.431-433
[11]Fig.7c, p.810-814
[13]Fig.6, p.17396-17398
[15]p.361-363
[16]Fig.5, p.696-697

references
[1]
CommentsX-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS).
PubMed ID9482715
JournalEMBO J
Year1998
Volume17
Pages1183-91
AuthorsHuang W, Jia J, Edwards P, Dehesh K, Schneider G, Lindqvist Y
TitleCrystal structure of beta-ketoacyl-acyl carrier protein synthase II from E.coli reveals the molecular architecture of condensing enzymes.
Related PDB1kas
Related Swiss-protP0AAI5
[2]
CommentsX-RAY CRYSTALLOGRAPHY (2.65 ANGSTROMS).
PubMed ID10037680
JournalJ Biol Chem
Year1999
Volume274
Pages6031-4
AuthorsMoche M, Schneider G, Edwards P, Dehesh K, Lindqvist Y
TitleStructure of the complex between the antibiotic cerulenin and its target, beta-ketoacyl-acyl carrier protein synthase.
Related PDB1b3n
Related Swiss-protP0AAI5
[3]
PubMed ID11171140
JournalBiochem Soc Trans
Year2000
Volume28
Pages601-7
Authorsvon Wettstein-Knowles P, Olsen J, Arnvig Mcguire K, Larsen S
TitleMolecular aspects of beta-ketoacyl synthase (KAS) catalysis.
[4]
CommentsX-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS).
PubMed ID10673437
JournalStructure
Year2000
Volume8
Pages185-95
AuthorsDavies C, Heath RJ, White SW, Rock CO
TitleThe 1.8 A crystal structure and active-site architecture of beta-ketoacyl-acyl carrier protein synthase III (FabH) from escherichia coli.
Related PDB1ebl
Related Swiss-protP0A6R0
[5]
PubMed ID11502177
JournalBiochemistry
Year2001
Volume40
Pages9836-45
AuthorsMcGuire KA, Siggaard-Andersen M, Bangera MG, Olsen JG, von Wettstein-Knowles P
Titlebeta-Ketoacyl-[acyl carrier protein] synthase I of Escherichia coli: aspects of the condensation mechanism revealed by analyses of mutations in the active site pocket.
[6]
CommentsX-RAY CRYSTALLOGRAPHY (1.54 ANGSTROMS).
PubMed ID11152607
JournalJ Mol Biol
Year2001
Volume305
Pages491-503
AuthorsMoche M, Dehesh K, Edwards P, Lindqvist Y
TitleThe crystal structure of beta-ketoacyl-acyl carrier protein synthase II from Synechocystis sp. at 1.54 A resolution and its relationship to other condensing enzymes.
Related PDB1e5m
Related Swiss-protP73283
[7]
PubMed ID12196027
JournalBiochemistry
Year2002
Volume41
Pages10877-87
AuthorsWitkowski A, Joshi AK, Smith S
TitleMechanism of the beta-ketoacyl synthase reaction catalyzed by the animal fatty acid synthase.
[8]
PubMed ID12837788
JournalJ Bacteriol
Year2003
Volume185
Pages4136-43
AuthorsPrice AC, Rock CO, White SW
TitleThe 1.3-Angstrom-resolution crystal structure of beta-ketoacyl-acyl carrier protein synthase II from Streptococcus pneumoniae.
Related PDB1ox0,1oxh
[9]
PubMed ID12866053
JournalProteins
Year2003
Volume52
Pages427-35
AuthorsDawe JH, Porter CT, Thornton JM, Tabor AB
TitleA template search reveals mechanistic similarities and differences in beta-ketoacyl synthases (KAS) and related enzymes.
[10]
PubMed ID15286722
JournalNat Struct Mol Biol
Year2004
Volume11
Pages888-93
AuthorsKeatinge-Clay AT, Maltby DA, Medzihradszky KF, Khosla C, Stroud RM
TitleAn antibiotic factory caught in action.
Related PDB1tqy
[11]
PubMed ID15952903
JournalAnnu Rev Biochem
Year2005
Volume74
Pages791-831
AuthorsWhite SW, Zheng J, Zhang YM, Rock
TitleThe structural biology of type II fatty acid biosynthesis.
[12]
PubMed ID16356722
JournalTrends Biochem Sci
Year2005
Volume31
Pages64-71
AuthorsHaapalainen AM, Merilainen G, Wierenga RK
TitleThe thiolase superfamily: condensing enzymes with diverse reaction specificities.
[13]
PubMed ID16618705
JournalJ Biol Chem
Year2006
Volume281
Pages17390-9
AuthorsZhang YM, Hurlbert J, White SW, Rock CO
TitleRoles of the active site water, histidine 303, and phenylalanine 396 in the catalytic mechanism of the elongation condensing enzyme of Streptococcus pneumoniae.
Related PDB2alm
[14]
PubMed ID16710421
JournalNature
Year2006
Volume441
Pages358-61
AuthorsWang J, Soisson SM, Young K, Shoop W, Kodali S, Galgoci A, Painter R, Parthasarathy G, Tang YS, Cummings R, Ha S, Dorso K, Motyl M, Jayasuriya H, Ondeyka J, Herath K, Zhang C, Hernandez L, Allocco J, Basilio A, Tormo JR, Genilloud O, Vicente F, Pelaez F, Colwell L, Lee SH, Michael B, Felcetto T, Gill C, Silver LL, Hermes JD, Bartizal K, Barrett J, Schmatz D, Becker JW, Cully D, Singh SB
TitlePlatensimycin is a selective FabF inhibitor with potent antibiotic properties.
Related PDB2gfv,2gfw,2gfx,2gfy
[15]
PubMed ID18453702
JournalActa Crystallogr Sect F Struct Biol Cryst Commun
Year2008
Volume64
Pages358-66
AuthorsBagautdinov B, Ukita Y, Miyano M, Kunishima N
TitleStructure of 3-oxoacyl-(acyl-carrier protein) synthase II from Thermus thermophilus HB8.
Related PDB1j3n
[16]
PubMed ID18824113
JournalMol Phylogenet Evol
Year2008
Volume49
Pages691-701
AuthorsJiang C, Kim SY, Suh DY
TitleDivergent evolution of the thiolase superfamily and chalcone synthase family.
[17]
PubMed ID19233644
JournalBioorg Med Chem Lett
Year2009
Volume19
Pages1623-7
AuthorsShen HC, Ding FX, Singh SB, Parthasarathy G, Soisson SM, Ha SN, Chen X, Kodali S, Wang J, Dorso K, Tata JR, Hammond ML, Maccoss M, Colletti SL
TitleSynthesis and biological evaluation of platensimycin analogs.
Related PDB3g0y,3g11
[18]
PubMed ID19581087
JournalBioorg Med Chem Lett
Year2009
Volume19
Pages4756-9
AuthorsSingh SB, Ondeyka JG, Herath KB, Zhang C, Jayasuriya H, Zink DL, Parthasarathy G, Becker JW, Wang J, Soisson SM
TitleIsolation, enzyme-bound structure and antibacterial activity of platencin A1 from Streptomyces platensis.
Related PDB3hnz,3ho2,3ho9,3i8p

comments
This enzyme belongs to thiolase superfamily (see [11] and [12]). This enzyme belongs to the subfamily of type I and type II of beta-ketoacyl-acyl-carrier protein synthase (KAS I & KAS II). This enzyme is KAS II, whereas the counterpart enzyme is KAS I (EC 2.3.1.41; D00824 in EzCatDB), with a similar catalytic site.
Moreover, its homologous enzymes, which belong to KAS III subfamily, use acetyl-CoA as primer substrate, instead of acyl-ACP (EC 2.3.1.180; D00825, D00826, D00867 in EzCatDB), unlike KAS I and KAS II.
According to the literatre, this enzyme catalyzes the following reactions:
(A) Transfer of acyl group from sulfur atom of acyl-ACP to catalytic cysteine (see [15]):
(A0) Lys335 modulates the activity of His303 and His340.
(A1) His340 (of 1b3n) may act as a general base to deprotonate the nucleophile, Cys163. (Helix dipole moment may also activate the cysteine sidechain.)
(A2) The activated thiol group of Cys163 makes a nucleophilic attack on the acyl group of acyl-ACP, leading to a transition-state (I00138). The oxyanion hole, composed of the mainchain amide groups of Cys163 and Phe400, stabilizes the negative charge of the oxyanion on the tetrahedral transition-state (I00138).
(A3) His303 may act as a general acid to protonate the leaving sulfur atom of ACP, generating an acyl group on Cys163 (I00139).
(B) Hydrolysis of carbon-carbon bond one of which is carboxyl carbon of malonyl-ACP,forming carbanion/enolate transition-state (I00134) (see [7] and [13]):
(B0) Lys335 modulates the activity of His303 and His340.
(B1) His303 acts as a general base to deprotonate a nearby water molecule to activate it.
(B2) The activated water makes a nucleophilic attack on the carboxyl carbon (C3), forming a tetrahedral transition-state (I00140).
(B3) The tetrahedral transition-state collapses, to form the carbanion/enolate transition-state (I00134) and to release bicarbonate. Here, His340 acts as a second oxyanion hole, to stabilize the negative charge on the enolate oxygen, which is generated during the formation of the carbanion at the C2 carbon of malonyl group (I00134).
(C) Transfer of acyl group from catalytic cysteine to carbanion on the transition-state (I00134):
(C0) Protonated His340 stabilizes the enol group of the transition-state (I00134).
(C1) The carbanion makes a nucleophilic attack on the acyl group of the intermediate (I00139), forming a tetrahedral transition-state (I00141). The oxyanion of the tetrahedral transition-state (I00141) is stabilized by the oxyanion hole composed of the mainchain amide groups of Cys163 and Phe400.
(C2) His340 may act as a general acid to protonate the leaving catalytic residue, Cys163.

createdupdated
2009-11-172012-07-24
Copyright: Nozomi Nagano, JST & CBRC-AIST
Funded by PRESTO/Japan Science and Technology Corporation (JST) (December 2001 - November 2004)
Funded by Grant-in-Aid for Publication of Scientific Research Results/Japan Society for the Promotion of Science (JSPS) (April 2005 - March 2006)
Funded by Grant-in-Aid for Scientific Research (B)/Japan Society for the Promotion of Science (JSPS) (April 2005 - March 2008)
Funded by BIRD/Japan Science and Technology Corporation (JST) (September 2005 - September 2010)
Funded by BIRD/Japan Science and Technology Corporation (JST) (October 2007 - September 2010)
Funded by Grant-in-Aid for Publication of Scientific Research Results/Japan Society for the Promotion of Science (JSPS) (April 2011 - March 2012)

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