PDBsum entry 4mz7

Hydrolase

PDB id: 4mz7

Contents

Protein chains

481 a.a.

Ligands

DGT ×5

DTP

Metals

_MG ×2

_ZN ×2

Waters ×819

PDB id:

4mz7

Name:

Hydrolase

Title:

Structural insight into dgtp-dependent activation of tetrameric samhd1 deoxynucleoside triphosphate triphosphohydrolase

Structure:

Deoxynucleoside triphosphate triphosphohydrolase samhd1. Chain: a, b. Fragment: unp residues 109-626. 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: 562

Resolution:

1.80Å R-factor: 0.196 R-free: 0.226

Authors:

C.Zhu,W.Gao,K.Zhao,X.Qin,Y.Zhang,X.Peng,L.Zhang,Y.Dong,W.Zhang,P.Li, W.Wei,Y.Gong,X.F.Yu

Key ref:

C.Zhu et al. (2013). Structural insight into dGTP-dependent activation of tetrameric SAMHD1 deoxynucleoside triphosphate triphosphohydrolase. Nat Commun, 4, 2722. PubMed id: 24217394 DOI: 10.1038/ncomms3722

Date:

29-Sep-13 Release date: 20-Nov-13

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 1 residue position (black cross)

Enzyme reactions

• Enzyme class: E.C.3.1.5.- - ?????

DOI no: 10.1038/ncomms3722

Nat Commun 4:2722 (2013)

PubMed id: 24217394

Structural insight into dGTP-dependent activation of tetrameric SAMHD1 deoxynucleoside triphosphate triphosphohydrolase.

C.Zhu, W.Gao, K.Zhao, X.Qin, Y.Zhang, X.Peng, L.Zhang, Y.Dong, W.Zhang, P.Li, W.Wei, Y.Gong, X.F.Yu.

ABSTRACT

SAMHD1 is a dGTP-activated deoxynucleoside triphosphate triphosphohydrolase (dNTPase) whose dNTPase activity has been linked to HIV/SIV restriction. The mechanism of its dGTP-activated dNTPase function remains unclear. Recent data also indicate that SAMHD1 regulates retrotransposition of LINE-1 elements. Here we report the 1.8-Å crystal structure of homotetrameric SAMHD1 in complex with the allosteric activator and substrate dGTP/dATP. The structure indicates the mechanism of dGTP-dependent tetramer formation, which requires the cooperation of three subunits and two dGTP/dATP molecules at each allosteric site. Allosteric dGTP binding induces conformational changes at the active site, allowing a more stable interaction with the substrate and explaining the dGTP-induced SAMHD1 dNTPase activity. Mutations of dGTP binding residues in the allosteric site affect tetramer formation, dNTPase activity and HIV-1 restriction. dGTP-triggered tetramer formation is also important for SAMHD1-mediated LINE-1 regulation. The structural and functional information provided here should facilitate future investigation of SAMHD1 function, including dNTPase activity, LINE-1 modulation and HIV-1 restriction.