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Publication Abstract from PubMed

The crystal structure of the NADH:quinone oxidoreductase PA1024 has been solved in complex with NAD(+) to 2.2 A resolution. The nicotinamide C4 is 3.6 A from the FMN N5 atom, with a suitable orientation for facile hydride transfer. NAD(+) binds in a folded conformation at the interface of the TIM-barrel domain and the extended domain of the enzyme. Comparison of the enzyme-NAD(+) structure with that of the ligand-free enzyme revealed a different conformation of a short loop (75-86) that is part of the NAD(+) -binding pocket. P78, P82, and P84 provide internal rigidity to the loop, whereas Q80 serves as an active site latch that secures the NAD(+) within the binding pocket. An interrupted helix consisting of two alpha-helices connected by a small three-residue loop binds the pyrophosphate moiety of NAD(+) . The adenine moiety of NAD(+) appears to pi-pi stack with Y261. Steric constraints between the adenosine ribose of NAD(+) , P78, and Q80, control the strict specificity of the enzyme for NADH. Charged residues do not play a role in the specificity of PA1024 for the NADH substrate.

Steric hindrance controls pyridine nucleotide specificity of a flavin-dependent NADH:quinone oxidoreductase.,Ball J, Reis RAG, Agniswamy J, Weber IT, Gadda G Protein Sci. 2019 Jan;28(1):167-175. doi: 10.1002/pro.3514. Epub 2018 Oct 31. PMID:30246917^[2]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.