2z6j
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(New page: 200px {{Structure |PDB= 2z6j |SIZE=350|CAPTION= <scene name='initialview01'>2z6j</scene>, resolution 2.30Å |SITE= <scene name='pdbsite=AC1:Ca+Binding+Site+F...)
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Revision as of 08:58, 2 April 2008
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| , resolution 2.30Å | |||||||
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| Sites: | , , , , , and | ||||||
| Ligands: | , , , | ||||||
| Activity: | [acyl-carrier-protein_reductase_(NADH) Enoyl-[acyl-carrier-protein] reductase (NADH)], with EC number 1.3.1.9 | ||||||
| Domains: | COG2070, NPD_like | ||||||
| Related: | 2Z6I
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| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
Crystal Structure of S. pneumoniae Enoyl-Acyl Carrier Protein Reductase (FabK) in Complex with an Inhibitor
Overview
Enoyl-acyl carrier protein (ACP) reductases are critical for bacterial type II fatty acid biosynthesis and thus are attractive targets for developing novel antibiotics. We determined the crystal structure of enoyl-ACP reductase (FabK) from Streptococcus pneumoniae at 1.7 A resolution. There was one dimer per asymmetric unit. Each subunit formed a triose phosphate isomerase (TIM) barrel structure, and flavin mononucleotide (FMN) was bound as a cofactor in the active site. The overall structure was similar to the enoyl-ACP reductase (ER) of fungal fatty acid synthase and to 2-nitropropane dioxygenase (2-ND) from Pseudomonas aeruginosa, although there were some differences among these structures. We determined the crystal structure of FabK in complex with a phenylimidazole derivative inhibitor to envision the binding site interactions. The crystal structure reveals that the inhibitor binds to a hydrophobic pocket in the active site of FabK, and this is accompanied by induced-fit movements of two loop regions. The thiazole ring and part of the ureido moiety of the inhibitor are involved in a face-to-face pi-pi stacking interaction with the isoalloxazine ring of FMN. The side-chain conformation of the proposed catalytic residue, His144, changes upon complex formation. Lineweaver-Burk plots indicate that the inhibitor binds competitively with respect to NADH, and uncompetitively with respect to crotonoyl coenzyme A. We propose that the primary basis of the inhibitory activity is competition with NADH for binding to FabK, which is the first step of the two-step ping-pong catalytic mechanism.
About this Structure
2Z6J is a Single protein structure of sequence from Streptococcus pneumoniae. Full crystallographic information is available from OCA.
Reference
Crystal structure of enoyl-acyl carrier protein reductase (FabK) from Streptococcus pneumoniae reveals the binding mode of an inhibitor., Saito J, Yamada M, Watanabe T, Iida M, Kitagawa H, Takahata S, Ozawa T, Takeuchi Y, Ohsawa F, Protein Sci. 2008 Apr;17(4):691-9. Epub 2008 Feb 27. PMID:18305197 [[Category: Enoyl-[acyl-carrier-protein] reductase (NADH)]]
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