PDBsum entry 6wcf

Hydrolase

PDB id: 6wcf

Contents

Protein chain

166 a.a.

Ligands

MES ×2

Waters ×197

References listed in PDB file

Key reference

• Title: Crystal structures of sars-Cov-2 ADP-Ribose phosphatase: from the apo form to ligand complexes.
• Authors: K.Michalska, Y.Kim, R.Jedrzejczak, N.I.Maltseva, L.Stols, M.Endres, A.Joachimiak.
• Ref.: IUCrJ, 2020, 7, 814-824. [DOI no: 10.1107/S2052252520009653]
• PubMed id: 32939273

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.