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

IUCrJ

Youngchang Kim¹  Robert Jedrzejczak¹  Natalia I. Maltseva¹  Karolina Michalska¹  Andrzej Joachimiak¹  Lucy Stols¹  Michael Endres² 

[1] Center for Structural Genomics of Infectious Diseases, Consortium for Advanced Science and Engineering, University of Chicago, Chicago, IL 60667, USA;Structural Biology Center, X-ray Science Division, Argonne National Laboratory, Argonne, IL 60439, USA;

关键词: sars-cov-2;    covid-19;    macrodomain;    adp-ribose phosphatase domain;    adrp;    nsp3;    mac1;    crystal structure;    adp-ribosylation;   

DOI  :  10.1107/S2052252520009653

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown