5LEW

DNA polymerase

Summary for 5LEW

• Entry DOI: 10.2210/pdb5lew/pdb
• Descriptor: DNA polymerase III subunit alpha, ZINC ION, SULFATE ION, ... (5 entities in total)
• Functional Keywords: dna polymerase multi-domain, transferase
• Biological source: Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv)
• Cellular location: Cytoplasm : P9WNT7
• Total number of polymer chains: 1
• Total formula weight: 103464.04

Authors

Banos-Mateos, S.,Lang, U.F.,Maslen, S.L.,Skehel, J.M.,Lamers, M.H. (deposition date: 2016-06-30, release date: 2017-10-25, Last modification date: 2024-01-10)

Primary citation

Banos-Mateos, S.,van Roon, A.M.,Lang, U.F.,Maslen, S.L.,Skehel, J.M.,Lamers, M.H.
High-fidelity DNA replication in Mycobacterium tuberculosis relies on a trinuclear zinc center.
Nat Commun, 8:855-855, 2017

PubMed Abstract: High-fidelity DNA replication depends on a proofreading 3'-5' exonuclease that is associated with the replicative DNA polymerase. The replicative DNA polymerase DnaE1 from the major pathogen Mycobacterium tuberculosis (Mtb) uses its intrinsic PHP-exonuclease that is distinct from the canonical DEDD exonucleases found in the Escherichia coli and eukaryotic replisomes. The mechanism of the PHP-exonuclease is not known. Here, we present the crystal structure of the Mtb DnaE1 polymerase. The PHP-exonuclease has a trinuclear zinc center, coordinated by nine conserved residues. Cryo-EM analysis reveals the entry path of the primer strand in the PHP-exonuclease active site. Furthermore, the PHP-exonuclease shows a striking similarity to E. coli endonuclease IV, which provides clues regarding the mechanism of action. Altogether, this work provides important insights into the PHP-exonuclease and reveals unique properties that make it an attractive target for novel anti-mycobacterial drugs.The polymerase and histidinol phosphatase (PHP) domain in the DNA polymerase DnaE1 is essential for mycobacterial high-fidelity DNA replication. Here, the authors determine the DnaE1 crystal structure, which reveals the PHP-exonuclease mechanism that can be exploited for antibiotic development.

PubMed: 29021523
DOI: 10.1038/s41467-017-00886-w

Experimental method

X-RAY DIFFRACTION (2.8 Å)