3DZK

Crystal structure of human CD38 extracellular domain, NMN complex

Summary for 3DZK

• Entry DOI: 10.2210/pdb3dzk/pdb
• Related: 3DZF 3DZG 3DZH 3DZI 3DZJ
• Descriptor: ADP-ribosyl cyclase 1, BETA-NICOTINAMIDE RIBOSE MONOPHOSPHATE (3 entities in total)
• Functional Keywords: nmn complex, beta sheets, alpha bundle, alternative splicing, diabetes mellitus, glycoprotein, hydrolase, membrane, nad, polymorphism, receptor, signal-anchor, transmembrane
• Biological source: Homo sapiens
• Cellular location: Membrane; Single-pass type II membrane protein: P28907
• Total number of polymer chains: 2
• Total formula weight: 61431.24

Authors

Liu, Q.,Kriksunov, I.A.,Jiang, H.,Graeff, R.,Lin, H.,Lee, H.C.,Hao, Q. (deposition date: 2008-07-29, release date: 2008-11-04, Last modification date: 2023-08-30)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (1.81 Å)