5mkw | pdb_00005mkw

Crystal structure of the human ZRANB3 HNH domain

spinqualitylabelsall models 5mkw, resolution 2.00Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 5mkw is a 2 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: GOL, ZN Gene: ZRANB3 (HUMAN) Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function [ZRAB3_HUMAN] DNA annealing helicase and endonuclease required to maintain genome stability at stalled or collapsed replication forks by facilitating fork restart and limiting inappropriate recombination that could occur during template switching events. Recruited to the sites of stalled DNA replication by polyubiquitinated PCNA and acts as a structure-specific endonuclease that cleaves the replication fork D-loop intermediate, generating an accessible 3'-OH group in the template of the leading strand, which is amenable to extension by DNA polymerase. In addition to endonuclease activity, also catalyzes the fork regression via annealing helicase activity in order to prevent disintegration of the replication fork and the formation of double-strand breaks. Publication Abstract from PubMed 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. Structural insights into the function of ZRANB3 in replication stress response.,Sebesta M, Cooper CDO, Ariza A, Carnie CJ, Ahel D Nat Commun. 2017 Jun 16;8:15847. doi: 10.1038/ncomms15847. PMID:28621305 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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