1Q7C

The structure of betaketoacyl-[ACP] reductase Y151F mutant in complex with NADPH fragment

Summary for 1Q7C

• Entry DOI: 10.2210/pdb1q7c/pdb
• Related: 1Q7B
• Descriptor: 3-oxoacyl-[acyl-carrier protein] reductase, NADPH DIHYDRO-NICOTINAMIDE-ADENINE-DINUCLEOTIDE PHOSPHATE (3 entities in total)
• Functional Keywords: oxoacyl reductase; nadp+; crystal structure, oxidoreductase
• Biological source: Escherichia coli
• Total number of polymer chains: 2
• Total formula weight: 52633.40

Authors

Price, A.C.,Zhang, Y.-M.,Rock, C.O.,White, S.M. (deposition date: 2003-08-17, release date: 2004-02-17, Last modification date: 2024-02-21)

Primary citation

Price, A.C.,Zhang, Y.-M.,Rock, C.O.,White, S.M.
Cofactor-Induced Conformational Rearrangements Establish a Catalytically Competent Active Site and a Proton Relay Conduit in FabG
Structure, 12:417-428, 2004

PubMed Abstract: beta-Ketoacyl-acyl carrier protein reductase (FabG) is a key component in the type II fatty acid synthase system. The structures of Escherichia coli FabG and the FabG[Y151F] mutant in binary complexes with NADP(H) reveal that mechanistically important conformational changes accompany cofactor binding. The active site Ser-Tyr-Lys triad is repositioned into a catalytically competent constellation, and a hydrogen bonded network consisting of ribose hydroxyls, the Ser-Tyr-Lys triad, and four water molecules creates a proton wire to replenish the tyrosine proton donated during catalysis. Also, a disordered loop in FabG forms a substructure in the complex that shapes the entrance to the active site. A key observation is that the nicotinamide portion of the cofactor is disordered in the FabG[Y151F].NADP(H) complex, and Tyr151 appears to be necessary for high-affinity cofactor binding. Biochemical data confirm that FabG[Y151F] is defective in NADPH binding. Finally, structural changes consistent with the observed negative cooperativity of FabG are described.

PubMed: 15016358
DOI: 10.1016/j.str.2004.02.008

Experimental method

X-RAY DIFFRACTION (2.5 Å)