PDBsum entry 4qg0

Hydrolase

PDB id: 4qg0

Contents

Protein chains

481 a.a.

Ligands

DGT ×4

DUT ×8

EDO

Metals

_MG ×7

Waters ×182

References listed in PDB file

Key reference

• Title: Structural basis of allosteric activation of sterile α motif and histidine-Aspartate domain-Containing protein 1 (samhd1) by nucleoside triphosphates.
• Authors: L.M.Koharudin, Y.Wu, M.Delucia, J.Mehrens, A.M.Gronenborn, J.Ahn.
• Ref.: J Biol Chem, 2014, 289, 32617-32627. [DOI no: 10.1074/jbc.M114.591958]
• PubMed id: 25288794

Abstract

Sterile α motif and histidine-aspartate domain-containing protein 1 (SAMHD1) plays a critical role in inhibiting HIV infection, curtailing the pool of dNTPs available for reverse transcription of the viral genome. Recent structural data suggested a compelling mechanism for the regulation of SAMHD1 enzymatic activity and revealed dGTP-induced association of two inactive dimers into an active tetrameric enzyme. Here, we present the crystal structures of SAMHD1 catalytic core (residues 113-626) tetramers, complexed with mixtures of nucleotides, including dGTP/dATP, dGTP/dCTP, dGTP/dTTP, and dGTP/dUTP. The combined structural and biochemical data provide insight into dNTP promiscuity at the secondary allosteric site and how enzymatic activity is modulated. In addition, we present biochemical analyses of GTP-induced SAMHD1 full-length tetramerization and the structure of SAMHD1 catalytic core tetramer in complex with GTP/dATP, revealing the structural basis of GTP-mediated SAMHD1 activation. Altogether, the data presented here advance our understanding of SAMHD1 function during cellular homeostasis.