PDBsum entry 6wcf

Hydrolase

PDB id: 6wcf

Contents

Protein chain

166 a.a.

Ligands

MES ×2

Waters ×197

PDB id:

6wcf

Name:

Hydrolase

Title:

Crystal structure of adp ribose phosphatase of nsp3 from sars-cov-2 in complex with mes

Structure:

Non-structural protein 3. Chain: a. Synonym: nsp3,adp ribose phosphatase,pl2-pro,papain-like protease, papain-like proteinase,pl-pro. Engineered: yes

Source:

Severe acute respiratory syndrome coronavirus 2. 2019-ncov. Organism_taxid: 2697049. Gene: rep, 1a-1b. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008.

Resolution:

1.07Å R-factor: 0.127 R-free: 0.154

Authors:

K.Michalska,Y.Kim,R.Jedrzejczak,N.Maltseva,M.Endres,A.Mesecar, A.Joachimiak,Center For Structural Genomics Of Infectious Diseases (Csgid)

Key ref:

K.Michalska et al. (2020). Crystal structures of SARS-CoV-2 ADP-ribose phosphatase: from the apo form to ligand complexes. IUCrJ, 7, 814-824. PubMed id: 32939273 DOI: 10.1107/S2052252520009653

Date:

30-Mar-20 Release date: 15-Apr-20

Protein chain

P0DTD1  (R1AB_SARS2) -

DOI no: 10.1107/S2052252520009653

IUCrJ 7:814-824 (2020)

PubMed id: 32939273

Crystal structures of SARS-CoV-2 ADP-ribose phosphatase: from the apo form to ligand complexes.

K.Michalska, Y.Kim, R.Jedrzejczak, N.I.Maltseva, L.Stols, M.Endres, A.Joachimiak.

ABSTRACT

Among 15 nonstructural proteins (Nsps), the newly emerging Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2) encodes a large, multidomain Nsp3. One of its units is the ADP-ribose phosphatase domain (ADRP; also known as the macrodomain, MacroD), which is believed to interfere with the host immune response. Such a function appears to be linked to the ability of the protein to remove ADP-ribose from ADP-ribosylated proteins and RNA, yet the precise role and molecular targets of the enzyme remain unknown. Here, five high-resolution (1.07-2.01 Å) crystal structures corresponding to the apo form of the protein and its complexes with 2-(N-morpholino)ethanesulfonic acid (MES), AMP and ADP-ribose have been determined. The protein is shown to undergo conformational changes to adapt to the ligand in the manner previously observed in close homologues from other viruses. A conserved water molecule is also identified that may participate in hydrolysis. This work builds foundations for future structure-based research on ADRP, including the search for potential antiviral therapeutics.