5W6Z

Crystal structure of the H24W mutant of HsNUDT16

Summary for 5W6Z

• Entry DOI: 10.2210/pdb5w6z/pdb
• Related: 5VY2 5W6X 5WJI 6B09
• Descriptor: U8 snoRNA-decapping enzyme, SODIUM ION (3 entities in total)
• Functional Keywords: nudix, nudix hydrolase, decapping enzyme, demodification of parylation, hydrolase
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 4
• Total formula weight: 85536.93

Authors

Thirawatananond, P.,Gabelli, S.B. (deposition date: 2017-06-18, release date: 2018-12-19, Last modification date: 2023-10-04)

Primary citation

Thirawatananond, P.,McPherson, R.L.,Malhi, J.,Nathan, S.,Lambrecht, M.J.,Brichacek, M.,Hergenrother, P.J.,Leung, A.K.L.,Gabelli, S.B.
Structural analyses of NudT16-ADP-ribose complexes direct rational design of mutants with improved processing of poly(ADP-ribosyl)ated proteins.
Sci Rep, 9:5940-5940, 2019

PubMed Abstract: ADP-ribosylation is a post-translational modification that occurs on chemically diverse amino acids, including aspartate, glutamate, lysine, arginine, serine and cysteine on proteins and is mediated by ADP-ribosyltransferases, including a subset commonly known as poly(ADP-ribose) polymerases. ADP-ribose can be conjugated to proteins singly as a monomer or in polymeric chains as poly(ADP-ribose). While ADP-ribosylation can be reversed by ADP-ribosylhydrolases, this protein modification can also be processed to phosphoribosylation by enzymes possessing phosphodiesterase activity, such as snake venom phosphodiesterase, mammalian ectonucleotide pyrophosphatase/phosphodiesterase 1, Escherichia coli RppH, Legionella pneumophila Sde and Homo sapiens NudT16 (HsNudT16). Our studies here sought to utilize X-ray crystallographic structures of HsNudT16 in complex with monomeric and dimeric ADP-ribose in identifying the active site for binding and processing free and protein-conjugated ADP-ribose into phosphoribose forms. These structural data guide rational design of mutants that widen the active site to better accommodate protein-conjugated ADP-ribose. We identified that several HsNudT16 mutants (Δ17, F36A, and F61S) have reduced activity for free ADP-ribose, similar processing ability against protein-conjugated mono(ADP-ribose), but improved catalytic efficiency for protein-conjugated poly(ADP-ribose). These HsNudT16 variants may, therefore, provide a novel tool to investigate different forms of ADP-ribose.

PubMed: 30976021
DOI: 10.1038/s41598-019-39491-w

Experimental method

X-RAY DIFFRACTION (2.61 Å)