Your browser doesn't support javascript.
ADP-ribose and analogues bound to the deMARylating macrodomain from the bat coronavirus HKU4.
Hammond, Robert G; Schormann, Norbert; McPherson, Robert Lyle; Leung, Anthony K L; Deivanayagam, Champion C S; Johnson, Margaret A.
  • Hammond RG; Department of Chemistry, University of Alabama at Birmingham, Birmingham, AL 35294.
  • Schormann N; Department of Biochemistry and Molecular Genetics, University of Alabama at Birmingham, Birmingham, AL 35294.
  • McPherson RL; Department of Biochemistry and Molecular Biology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD 21205.
  • Leung AKL; Department of Biochemistry and Molecular Biology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD 21205.
  • Deivanayagam CCS; Department of Molecular Biology and Genetics, School of Medicine, Johns Hopkins University, Baltimore, MD 21205.
  • Johnson MA; Department of Oncology, School of Medicine, Johns Hopkins University, Baltimore, MD 21287.
Proc Natl Acad Sci U S A ; 118(2)2021 01 12.
Article in English | MEDLINE | ID: covidwho-1006583
ABSTRACT
Macrodomains are proteins that recognize and hydrolyze ADP ribose (ADPR) modifications of intracellular proteins. Macrodomains are implicated in viral genome replication and interference with host cell immune responses. They are important to the infectious cycle of Coronaviridae and Togaviridae viruses. We describe crystal structures of the conserved macrodomain from the bat coronavirus (CoV) HKU4 in complex with ligands. The structures reveal a binding cavity that accommodates ADPR and analogs via local structural changes within the pocket. Using a radioactive assay, we present evidence of mono-ADPR (MAR) hydrolase activity. In silico analysis presents further evidence on recognition of the ADPR modification for hydrolysis. Mutational analysis of residues within the binding pocket resulted in diminished enzymatic activity and binding affinity. We conclude that the common structural features observed in the macrodomain in a bat CoV contribute to a conserved function that can be extended to other known macrodomains.
Subject(s)
Keywords

Full text: Available Collection: International databases Database: MEDLINE Main subject: Pyrophosphatases / Adenosine Diphosphate Ribose / Viral Nonstructural Proteins / Coronavirus Limits: Animals Language: English Year: 2021 Document Type: Article

Similar

MEDLINE

...
LILACS

LIS


Full text: Available Collection: International databases Database: MEDLINE Main subject: Pyrophosphatases / Adenosine Diphosphate Ribose / Viral Nonstructural Proteins / Coronavirus Limits: Animals Language: English Year: 2021 Document Type: Article