5MKW
Crystal structure of the human ZRANB3 HNH domain
Summary for 5MKW
| Entry DOI | 10.2210/pdb5mkw/pdb |
| Descriptor | DNA annealing helicase and endonuclease ZRANB3, ZINC ION, GLYCEROL, ... (4 entities in total) |
| Functional Keywords | endonuclease, metalloprotein, zinc-binding, dna-binding, hydrolase |
| Biological source | Homo sapiens (Human) |
| Total number of polymer chains | 2 |
| Total formula weight | 28519.11 |
| Authors | Ariza, A. (deposition date: 2016-12-05, release date: 2017-06-28, Last modification date: 2024-05-01) |
| Primary citation | Sebesta, M.,Cooper, C.D.O.,Ariza, A.,Carnie, C.J.,Ahel, D. Structural insights into the function of ZRANB3 in replication stress response. Nat Commun, 8:15847-15847, 2017 Cited by PubMed Abstract: Strategies to resolve replication blocks are critical for the maintenance of genome stability. Among the factors implicated in the replication stress response is the ATP-dependent endonuclease ZRANB3. Here, we present the structure of the ZRANB3 HNH (His-Asn-His) endonuclease domain and provide a detailed analysis of its activity. We further define PCNA as a key regulator of ZRANB3 function, which recruits ZRANB3 to stalled replication forks and stimulates its endonuclease activity. Finally, we present the co-crystal structures of PCNA with two specific motifs in ZRANB3: the PIP box and the APIM motif. Our data provide important structural insights into the PCNA-APIM interaction, and reveal unexpected similarities between the PIP box and the APIM motif. We propose that PCNA and ATP-dependency serve as a multi-layered regulatory mechanism that modulates ZRANB3 activity at replication forks. Importantly, our findings allow us to interpret the functional significance of cancer associated ZRANB3 mutations. PubMed: 28621305DOI: 10.1038/ncomms15847 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2 Å) |
Structure validation
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