6WCF

Crystal Structure of ADP ribose phosphatase of NSP3 from SARS-CoV-2 in complex with MES

Summary for 6WCF

• Entry DOI: 10.2210/pdb6wcf/pdb
• Related: 6VXS 6w02 6w6y
• Descriptor: Non-structural protein 3, 2-(N-MORPHOLINO)-ETHANESULFONIC ACID (3 entities in total)
• Functional Keywords: sars coronavirus, structural genomics, center for structural genomics of infectious diseases, csgid, viral protein, hydrolase
• Biological source: Severe acute respiratory syndrome coronavirus 2 (2019-nCoV)
• Total number of polymer chains: 1
• Total formula weight: 18666.24

Authors

Michalska, K.,Kim, Y.,Jedrzejczak, R.,Maltseva, N.,Endres, M.,Mesecar, A.,Joachimiak, A.,Center for Structural Genomics of Infectious Diseases (CSGID) (deposition date: 2020-03-30, release date: 2020-04-15, Last modification date: 2023-10-18)

Primary citation

Michalska, K.,Kim, Y.,Jedrzejczak, R.,Maltseva, N.I.,Stols, L.,Endres, M.,Joachimiak, A.
Crystal structures of SARS-CoV-2 ADP-ribose phosphatase: from the apo form to ligand complexes.
Iucrj, 7:814-824, 2020

PubMed 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-(-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.

PubMed: 32939273
DOI: 10.1107/S2052252520009653

Experimental method

X-RAY DIFFRACTION (1.065 Å)