PMID- 10037680
OWN - NLM
STAT- MEDLINE
DCOM- 19990330
LR  - 20240109
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 274
IP  - 10
DP  - 1999 Mar 5
TI  - Structure of the complex between the antibiotic cerulenin and its target, 
      beta-ketoacyl-acyl carrier protein synthase.
PG  - 6031-4
AB  - In the biosynthesis of fatty acids, the beta-ketoacyl-acyl carrier protein (ACP) 
      synthases catalyze chain elongation by the addition of two-carbon units derived 
      from malonyl-ACP to an acyl group bound to either ACP or CoA. The enzyme is a 
      possible drug target for treatment of certain cancers and for tuberculosis. The 
      crystal structure of the complex of the enzyme from Escherichia coli, and the 
      fungal mycotoxin cerulenin reveals that the inhibitor is bound in a hydrophobic 
      pocket formed at the dimer interface. Cerulenin is covalently attached to the 
      active site cysteine through its C2 carbon atom. The fit of the inhibitor to the 
      active site is not optimal, and there is thus room for improvement through 
      structure based design.
FAU - Moche, M
AU  - Moche M
AD  - Department of Medical Biochemistry and Biophysics, Doktorsringen 9A1, Karolinska 
      Institutet, S-171 77 Stockholm, Sweden.
FAU - Schneider, G
AU  - Schneider G
FAU - Edwards, P
AU  - Edwards P
FAU - Dehesh, K
AU  - Dehesh K
FAU - Lindqvist, Y
AU  - Lindqvist Y
LA  - eng
SI  - PDB/1B3N
SI  - PDB/R1BNSF
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (Antifungal Agents)
RN  - 0 (Isoenzymes)
RN  - 17397-89-6 (Cerulenin)
RN  - EC 2.3.1.- (beta-ketoacyl-acyl carrier protein synthase I)
RN  - EC 2.3.1.41 (3-Oxoacyl-(Acyl-Carrier-Protein) Synthase)
SB  - IM
MH  - 3-Oxoacyl-(Acyl-Carrier-Protein) Synthase/*chemistry/metabolism
MH  - Antifungal Agents/chemistry/metabolism
MH  - Binding Sites
MH  - Cerulenin/*chemistry/metabolism
MH  - Escherichia coli
MH  - Isoenzymes/*chemistry/metabolism
MH  - Molecular Sequence Data
MH  - Protein Binding
MH  - Protein Conformation
MH  - Substrate Specificity
EDAT- 1999/02/26 00:00
MHDA- 1999/02/26 00:01
CRDT- 1999/02/26 00:00
PHST- 1999/02/26 00:00 [pubmed]
PHST- 1999/02/26 00:01 [medline]
PHST- 1999/02/26 00:00 [entrez]
AID - S0021-9258(19)87549-X [pii]
AID - 10.1074/jbc.274.10.6031 [doi]
PST - ppublish
SO  - J Biol Chem. 1999 Mar 5;274(10):6031-4. doi: 10.1074/jbc.274.10.6031.