4I08

Crystal structure of beta-ketoacyl-acyl carrier protein reductase (FabG) from Vibrio cholerae in complex with NADPH

4I08 の概要

• エントリーDOI: 10.2210/pdb4i08/pdb
• 分子名称: 3-oxoacyl-[acyl-carrier-protein] reductase FabG, SULFATE ION, 1,2-ETHANEDIOL, ... (5 entities in total)
• 機能のキーワード: structural genomics, center for structural genomics of infectious diseases, csgid, vibrio cholerae, fabg, rossmann fold, beta-ketoacyl-acyl carrier protein reductase, short chain dehydrogenase, nadp(h), oxidoreductase
• 由来する生物種: Vibrio cholerae O1
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 55291.83

構造登録者

Hou, J.,Chruszcz, M.,Zheng, H.,Osinski, T.,Anderson, W.F.,Minor, W.,Center for Structural Genomics of Infectious Diseases (CSGID) (登録日: 2012-11-16, 公開日: 2012-12-12, 最終更新日: 2023-09-20)

主引用文献

Hou, J.,Zheng, H.,Chruszcz, M.,Zimmerman, M.D.,Shumilin, I.A.,Osinski, T.,Demas, M.,Grimshaw, S.,Minor, W.
Dissecting the Structural Elements for the Activation of beta-Ketoacyl-(Acyl Carrier Protein) Reductase from Vibrio cholerae.
J.Bacteriol., 198:463-476, 2015

PubMed Abstract: β-Ketoacyl-(acyl carrier protein) reductase (FabG) catalyzes the key reductive reaction in the elongation cycle of fatty acid synthesis (FAS), which is a vital metabolic pathway in bacteria and a promising target for new antibiotic development. The activation of the enzyme is usually linked to the formation of a catalytic triad and cofactor binding, and crystal structures of FabG from different organisms have been captured in either the active or inactive conformation. However, the structural elements which enable activation of FabG require further exploration. Here we report the findings of structural, enzymatic, and binding studies of the FabG protein found in the causative agent of cholera, Vibrio cholerae (vcFabG). vcFabG exists predominantly as a dimer in solution and is able to self-associate to form tetramers, which is the state seen in the crystal structure. The formation of the tetramer may be promoted by the presence of the cofactor NADP(H). The transition between the dimeric and tetrameric states of vcFabG is related to changes in the conformations of the α4/α5 helices on the dimer-dimer interface. Two glycine residues adjacent to the dimer interface (G92 and G141) are identified to be the hinge for the conformational changes, while the catalytic tyrosine (Y155) and a glutamine residue that forms hydrogen bonds to both loop β4-α4 and loop β5-α5 (Q152) stabilize the active conformation. The functions of the aforementioned residues were confirmed by binding and enzymatic assays for the corresponding mutants.

PubMed: 26553852
DOI: 10.1128/JB.00360-15

実験手法

X-RAY DIFFRACTION (2.063 Å)