4ZCC

Renalase in complex with NADH

4ZCC の概要

• エントリーDOI: 10.2210/pdb4zcc/pdb
• 分子名称: Renalase, FLAVIN-ADENINE DINUCLEOTIDE, 1,4-DIHYDRONICOTINAMIDE ADENINE DINUCLEOTIDE, ... (5 entities in total)
• 機能のキーワード: renalase, oxidase, flavoenzyme, oxidoreductase
• 由来する生物種: Pseudomonas syringae pv. phaseolicola (strain 1448A / Race 6)
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 153405.80

構造登録者

Silvaggi, N.R.,Moran, G.R.,Roman, J.V. (登録日: 2015-04-15, 公開日: 2015-07-15, 最終更新日: 2023-09-27)

主引用文献

Hoag, M.R.,Roman, J.,Beaupre, B.A.,Silvaggi, N.R.,Moran, G.R.
Bacterial Renalase: Structure and Kinetics of an Enzyme with 2- and 6-Dihydro-beta-NAD(P) Oxidase Activity from Pseudomonas phaseolicola.
Biochemistry, 54:3791-3802, 2015

PubMed Abstract: Despite a lack of convincing in vitro evidence and a number of sound refutations, it is widely accepted that renalase is an enzyme unique to animals that catalyzes the oxidative degradation of catecholamines in blood in order to lower vascular tone. Very recently, we identified isomers of β-NAD(P)H as substrates for renalase (Beaupre, B. A. et al. (2015) Biochemistry, 54, 795-806). These molecules carry the hydride equivalent on the 2 or 6 position of the nicotinamide base and presumably arise in nonspecific redox reactions of nicotinamide dinucleotides. Renalase serves to rapidly oxidize these isomers to form β-NAD(P)⁺ and then pass the electrons to dioxygen, forming H₂O₂. We have also shown that these substrate molecules are highly inhibitory to dehydrogenase enzymes and thus have proposed an intracellular metabolic role for this enzyme. Here, we identify a renalase from an organism without a circulatory system. This bacterial form of renalase has the same substrate specificity profile as that of human renalase but, in terms of binding constant (K(d)), shows a marked preference for substrates derived from β-NAD⁺. 2-dihydroNAD(P) substrates reduce the enzyme with rate constants (k(red)) that greatly exceed those for 6-dihydroNAD(P) substrates. Taken together, k(red)/K(d) values indicate a minimum 20-fold preference for 2DHNAD. We also offer the first structures of a renalase in complex with catalytically relevant ligands β-NAD⁺ and β-NADH (the latter being an analogue of the substrate(s)). These structures show potential electrostatic repulsion interactions with the product and a unique binding orientation for the substrate nicotinamide base that is consistent with the identified activity.

PubMed: 26016690
DOI: 10.1021/acs.biochem.5b00451

実験手法

X-RAY DIFFRACTION (1.997 Å)