6LH4

Crystal structural of MacroD1-ADPr complex

Summary for 6LH4

• Entry DOI: 10.2210/pdb6lh4/pdb
• Descriptor: ADP-ribose glycohydrolase MACROD1, [(2R,3S,4R,5R)-5-(6-AMINOPURIN-9-YL)-3,4-DIHYDROXY-OXOLAN-2-YL]METHYL [HYDROXY-[[(2R,3S,4R,5S)-3,4,5-TRIHYDROXYOXOLAN-2-YL]METHOXY]PHOSPHORYL] HYDROGEN PHOSPHATE (3 entities in total)
• Functional Keywords: macrod1, adpr, catalysis, dna repair, hydrolase
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 4
• Total formula weight: 107679.22

Authors

Yang, X.,Ma, Y.,Li, Y. (deposition date: 2019-12-06, release date: 2020-12-09, Last modification date: 2023-11-29)

Primary citation

Yang, X.,Ma, Y.,Li, Y.,Dong, Y.,Yu, L.L.,Wang, H.,Guo, L.,Wu, C.,Yu, X.,Liu, X.
Molecular basis for the MacroD1-mediated hydrolysis of ADP-ribosylation.
DNA Repair (Amst), 94:102899-102899, 2020

PubMed Abstract: MacroD1 is an enzyme that hydrolyzes protein mono-ADP-ribosylation. However, the key catalytic residues of MacroD1 in these biochemical reactions remain elusive. Here, we present the crystal structure of MacroD1 in a complex with ADP-ribose (ADPR). The β5-α10-loop functions as a switch loop to mediate substrate recognition and right orientation. The conserved Phe in the β5-α10-loop plays a crucial role in the orientation of ADPR distal ribose, and a conserved hydrogen-bond network contributes significantly to hold and orient the catalytic water12, which mediates ADPR hydrolysis. Moreover, we found that MacroD1 was recruited to the sites of DNA damage via recognition of ADP-ribosylation at DNA lesions. The MacroD1-mediated ADPR hydrolysis is essential for DNA damage repair. Taken together, our study provides structural and functional insights into the molecular mechanism of MacroD1-mediated ADPR hydrolysis and its role in DNA damage repair.

PubMed: 32683309
DOI: 10.1016/j.dnarep.2020.102899

Experimental method

X-RAY DIFFRACTION (1.999 Å)