4NK5

Crystal structure of FabI-NAD complex from Candidatus Liberibacter asiaticus

Summary for 4NK5

• Entry DOI: 10.2210/pdb4nk5/pdb
• Related: 4NK4
• Descriptor: Enoyl-[acyl-carrier-protein] reductase [NADH], NICOTINAMIDE-ADENINE-DINUCLEOTIDE (3 entities in total)
• Functional Keywords: enoyl-acp reductase i, oxidoreductase
• Biological source: Candidatus Liberibacter asiaticus
• Total number of polymer chains: 6
• Total formula weight: 200849.22

Authors

Jiang, L.,Gao, Z.Q.,Dong, Y.H. (deposition date: 2013-11-12, release date: 2014-02-12, Last modification date: 2023-09-20)

Primary citation

Jiang, L.,Gao, Z.,Li, Y.,Wang, S.,Dong, Y.
Crystal structures and kinetic properties of enoyl-acyl carrier protein reductase I from Candidatus Liberibacter asiaticus.
Protein Sci., 23:366-377, 2014

PubMed Abstract: Huanglongbing (HLB) is a destructive citrus disease. The leading cause of HLB is Candidatus Liberibacter asiaticus. Fatty acid biosynthesis is essential for bacterial viability and has been validated as a target for the discovery of novel antibacterial agents. Enoyl-acyl carrier protein reductase (also called ENR or FabI and a product of the fabI gene) is an enzyme required in a critical step of bacterial fatty acid biosynthesis and has attracted attention as a target of novel antimicrobial agents. We determined the crystal structures of FabI from Ca. L. asiaticus in its apoform as well as in complex with b-nicotinamide adenine dinucleotide (NAD) at 1.7 and 2.7 Å resolution, respectively, to facilitate the design and screening of small molecule inhibitors of FabI. The monomeric ClFabI is highly similar to other known FabI structures as expected; however, unlike the typical tetramer, ClFabI exists as a hexamer in crystal, whereas as dimer in solution, on the other hand, the substrate binding loop which always disordered in apoform FabI structures is ordered in apo-ClFabI. Interestingly, the structure of ClFabI undergoes remarkable conformational change in the substrate-binding loop in the presence of NAD. We conclude that the signature sequence motif of FabI can be considered as Gly-(Xaa)5-Ser-(Xaa)n-Val-Tyr-(Xaa)6-Lys-(Xaa)n-Thr instead of Tyr-(Xaa)6-Lys. We have further identified isoniazid as a competitive inhibitor with NADH.

PubMed: 24407918
DOI: 10.1002/pro.2418

Experimental method

X-RAY DIFFRACTION (2.7 Å)