3DZF

Crystal structure of human CD38 extracellular domain complexed with a covalent intermediate, ara-F-ribose-5'-phosphate

3DZF の概要

• エントリーDOI: 10.2210/pdb3dzf/pdb
• 関連するPDBエントリー: 3DZG 3DZH 3DZI 3DZJ 3DZK
• 分子名称: ADP-ribosyl cyclase 1, 2-deoxy-2-fluoro-5-O-phosphono-alpha-D-arabinofuranose (3 entities in total)
• 機能のキーワード: covalent intermediate, beta sheets, alpha bundle, diabetes mellitus, glycoprotein, hydrolase, membrane, nad, receptor, signal-anchor, transmembrane
• 由来する生物種: Homo sapiens
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 183674.96

構造登録者

Liu, Q.,Kriksunov, I.A.,Jiang, H.,Graeff, R.,Lin, H.,Lee, H.C.,Hao, Q. (登録日: 2008-07-29, 公開日: 2008-11-04, 最終更新日: 2024-10-16)

主引用文献

Liu, Q.,Kriksunov, I.A.,Jiang, H.,Graeff, R.,Lin, H.,Lee, H.C.,Hao, Q.
Covalent and Noncovalent Intermediates of an NAD Utilizing Enzyme, Human CD38.
Chem.Biol., 15:1068-1078, 2008

PubMed Abstract: Enzymatic utilization of nicotinamide adenine dinucleotide (NAD) has increasingly been shown to have fundamental roles in gene regulation, signal transduction, and protein modification. Many of the processes require the cleavage of the nicotinamide moiety from the substrate and the formation of a reactive intermediate. Using X-ray crystallography, we show that human CD38, an NAD-utilizing enzyme, is capable of catalyzing the cleavage reactions through both covalent and noncovalent intermediates, depending on the substrate used. The covalent intermediate is resistant to further attack by nucleophiles, resulting in mechanism-based enzyme inactivation. The noncovalent intermediate is stabilized mainly through H-bond interactions, but appears to remain reactive. Our structural results favor the proposal of a noncovalent intermediate during normal enzymatic utilization of NAD by human CD38 and provide structural insights into the design of covalent and noncovalent inhibitors targeting NAD-utilization pathways.

PubMed: 18940667
DOI: 10.1016/j.chembiol.2008.08.007

実験手法

X-RAY DIFFRACTION (2.01 Å)