2faq

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spinqualitylabelsall models 2faq, resolution 1.90Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image

Crystal Structure of Pseudomonas aeruginosa LigD polymerase domain with ATP and Manganese

Overview

DNA ligase D (LigD) is a large polyfunctional protein that participates in, a recently discovered pathway of nonhomologous end-joining in bacteria., LigD consists of an ATP-dependent ligase domain fused to a polymerase, domain (Pol) and a phosphoesterase module. The Pol activity is remarkable, for its dependence on manganese, its ability to perform templated and, nontemplated primer extension reactions, and its preference for adding, ribonucleotides to blunt DNA ends. Here we report the 1.5-A crystal, structure of the Pol domain of Pseudomonas LigD and its complexes with, manganese and ATP/dATP substrates, which reveal a minimized polymerase, with a two-metal mechanism and a fold similar to that of archaeal DNA, primase. Mutational analysis highlights the functionally relevant atomic, contacts in the active site. Although distinct nucleoside conformations, and contacts for ATP versus dATP are observed in the cocrystals, the, functional analysis suggests that the ATP-binding mode is the productive, conformation for dNMP and rNMP incorporation. We find that a mutation of, Mycobacterium LigD that uniquely ablates the polymerase activity results, in increased fidelity of blunt-end double-strand break repair in vivo by, virtue of eliminating nucleotide insertions at the recombination, junctions. Thus, LigD Pol is a direct catalyst of mutagenic nonhomologous, end-joining in vivo. Our studies underscore a previously uncharacterized, role for the primase-like polymerase family in DNA repair.

About this Structure

2FAQ is a Single protein structure of sequence from Pseudomonas aeruginosa with , and as ligands. Full crystallographic information is available from OCA.

Reference

Atomic structure and nonhomologous end-joining function of the polymerase component of bacterial DNA ligase D., Zhu H, Nandakumar J, Aniukwu J, Wang LK, Glickman MS, Lima CD, Shuman S, Proc Natl Acad Sci U S A. 2006 Feb 7;103(6):1711-6. Epub 2006 Jan 30. PMID:16446439

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