4NSP

Crystal structure of human ENDOV

Summary for 4NSP

• Entry DOI: 10.2210/pdb4nsp/pdb
• Descriptor: Endonuclease V (2 entities in total)
• Functional Keywords: raase h-like motif, hydrolase
• Biological source: Homo sapiens (human)
• Cellular location: Cytoplasm: Q8N8Q3
• Total number of polymer chains: 1
• Total formula weight: 27936.40

Authors

Xie, W.,Zhang, Z.,Hao, Z. (deposition date: 2013-11-28, release date: 2014-09-10, Last modification date: 2023-09-20)

Primary citation

Zhang, Z.,Hao, Z.,Wang, Z.,Li, Q.,Xie, W.
Structure of human endonuclease V as an inosine-specific ribonuclease.
Acta Crystallogr.,Sect.D, 70:2286-2294, 2014

PubMed Abstract: The 6-aminopurine ring of adenosine (A) can be deaminated to form the 6-oxopurine of inosine (I). Endonuclease Vs (EndoVs) are inosine-specific nucleases that cleave at the second phosphodiester bond 3' to inosine. EndoV proteins are highly conserved in all domains of life, but the bacterial and human enzymes seem to display distinct substrate preferences. While the bacterial enzymes exhibit high cleavage efficiency on various nucleic acid substrates, human EndoV (hEndoV) is most active towards ssRNA but is much less active towards other substrates. However, the structural basis of substrate recognition by hEndoV is not well understood. In this study, the 2.3 Å resolution crystal structure of hEndoV was determined and its unusual RNA-cleaving properties were investigated. The enzyme preserves the general `RNase H-like' structure, especially in the wedge motif, the metal-binding site and the hypoxanthine-binding pocket. hEndoV also features several extra insertions and a characteristic four-cysteine motif, in which Cys227 and Cys228, two cysteines that are highly conserved in higher eukaryotes, play important roles in catalysis. The structure presented here helps in understanding the substrate preference of hEndoV catalysis.

PubMed: 25195743
DOI: 10.1107/S139900471401356X

Experimental method

X-RAY DIFFRACTION (2.3 Å)