Bainbridge Island, WA, November 26, 2008 –deCODE biostructures (www.decodechembio.com) announced today they have elucidated the three-dimensional structure of an enzyme needed for DNA replication in Gram-positive bacteria.
Research published today in the Proceedings of the National Academy of Sciences (PNAS, Dec 30, 2008, vol. 105, no. 52, 20695-20700) of the United States of America, entitled “Structure of PolC Reveals Unique DNA Binding and Fidelity Determinants” details the 2.4 Angstrom resolution X-ray crystal structure of DNA polymerase IIIC (PolC) from Geobacillus kaustophilus. These findings reveal a snap-shot view of how the nucleotide substrate interacts with the enzyme’s active site while it is bound to DNA template. This detailed understanding of the G. kaustophilus PolC structure should aid drug design of new antibiotics that target the closely related PolC enzymes from pathogenic organisms such as Staphylococcus aureus and Streptococcus pyogenes. The structure is a first of its kind and gives the highest resolution detail of any type-III polymerase ternary complex structure solved to date. The PolC project was conducted as a collaboration with Replidyne, Inc. (www.replidyne.com) who utilized the contract research services of deCODE biostructures to provide three dimensional structures to support anti-infective development. “We are fortunate to have the opportunity to collaborate on difficult problems and generate X-ray crystal structures which provide a unique understanding of a fundamental biological process and aid in developing new antibiotics” said Alex Burgin, COO at deCODE biostructures.
The PolC structural information has beem made publicly available through the Protein Data Bank (www.rcsb.org/pdb, PDB IDs: 3F2B, 3F2C and 3F2D).
About deCODE biostructures
deCODE chemistry & biostructures provide contract research services to pharmaceutical companies, biotechnology companies, academic institutions, and government facilities. We take a collaborative approach to pharmaceutical research services through a seamless integration of chemistry and biology capabilities including protein production, multifaceted structural studies, X-ray crystallography, lead identification, ex vivo and in vivo assays, cGMP manufacturing and regulatory capabilities. These integrated capabilities enable accelerated timelines for moving molecules from the concept and into the clinic. Visit deCODE chemistry & biostructures on the web at www.decodechembio.com.
deCODE gratefully acknowledges the funding and protein biochemistry support from Replidyne, and also from the National Institute of Allergy and Infectious Disease (NIAID) which supports the Seattle Structural Genomics Center for Infectious Disease (www.SSGCID.org) through Contract HHSN266200700057C.
Cartoon representation of the PolC-DNA structure. Green ribbons represent the polypeptide backbone of the PolC protein, gold stick structures represent the bound DNA and the red space-filling object is the dGTP substrate.
