PDBsum entry 4qfx

Hydrolase

PDB id: 4qfx

Contents

Protein chains

481 a.a.

Ligands

DGT ×8

DTP ×4

Metals

_MG ×8

Waters ×384

PDB id:

4qfx

Name:

Hydrolase

Title:

Crystal structure of the tetrameric dgtp/datp-bound samhd1 (rn206) mutant catalytic core

Structure:

Deoxynucleoside triphosphate triphosphohydrolase samhd1. Chain: a, b, c, d. Fragment: unp residues 113-626. Synonym: dntpase, dendritic cell-derived ifng-induced protein, dcip, monocyte protein 5, mop-5, sam domain and hd domain-containing protein 1. Engineered: yes. Mutation: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: samhd1, mop5. Expressed in: escherichia coli. Expression_system_taxid: 469008.

Resolution:

2.20Å R-factor: 0.229 R-free: 0.270

Authors:

L.M.I.Koharudin,Y.Wu,M.Delucia,J.Mehrens,A.M.Gronenborn,J.Ahn

Key ref:

L.M.Koharudin et al. (2014). Structural basis of allosteric activation of sterile α motif and histidine-aspartate domain-containing protein 1 (SAMHD1) by nucleoside triphosphates. J Biol Chem, 289, 32617-32627. PubMed id: 25288794 DOI: 10.1074/jbc.M114.591958

Date:

21-May-14 Release date: 15-Oct-14

Protein chains

Q9Y3Z3  (SAMH1_HUMAN) -  Deoxynucleoside triphosphate triphosphohydrolase SAMHD1 from Homo sapiens

Seq: 626 a.a.

Struc: 481 a.a.*

* PDB and UniProt seqs differ at 2 residue positions (black crosses)

Enzyme reactions

• Enzyme class: E.C.3.1.5.- - ?????

DOI no: 10.1074/jbc.M114.591958

J Biol Chem 289:32617-32627 (2014)

PubMed id: 25288794

Structural basis of allosteric activation of sterile α motif and histidine-aspartate domain-containing protein 1 (SAMHD1) by nucleoside triphosphates.

L.M.Koharudin, Y.Wu, M.DeLucia, J.Mehrens, A.M.Gronenborn, J.Ahn.

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.