5U8H

DNA Polymerase Beta G231D crystallized in PEG 400

Summary for 5U8H

• Entry DOI: 10.2210/pdb5u8h/pdb
• Related: 5U8G 5U8I
• Descriptor: DNA polymerase beta, DNA (5'-D(*CP*CP*GP*AP*CP*AP*GP*CP*GP*CP*AP*TP*CP*AP*GP*C)-3'), DNA (5'-D(*GP*CP*TP*GP*AP*TP*GP*CP*GP*C)-3'), ... (6 entities in total)
• Functional Keywords: dna polymerase, lyase, dna complex, transferase, lyase-dna complex, lyase/dna
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 4
• Total formula weight: 47795.88

Authors

Eckenroth, B.E.,Doublie, S. (deposition date: 2016-12-14, release date: 2017-04-26, Last modification date: 2023-10-04)

Primary citation

Eckenroth, B.E.,Towle-Weicksel, J.B.,Nemec, A.A.,Murphy, D.L.,Sweasy, J.B.,Doublie, S.
Remote Mutations Induce Functional Changes in Active Site Residues of Human DNA Polymerase beta.
Biochemistry, 56:2363-2371, 2017

PubMed Abstract: With the formidable growth in the volume of genetic information, it has become essential to identify and characterize mutations in macromolecules not only to predict contributions to disease processes but also to guide the design of therapeutic strategies. While mutations of certain residues have a predictable phenotype based on their chemical nature and known structural position, many types of mutations evade prediction based on current information. Described in this work are the crystal structures of two cancer variants located in the palm domain of DNA polymerase β (pol β), S229L and G231D, whose biological phenotype was not readily linked to a predictable structural implication. Structural results demonstrate that the mutations elicit their effect through subtle influences on secondary interactions with a residue neighboring the active site. Residues 229 and 231 are 7.5 and 12.5 Å, respectively, from the nearest active site residue, with a β-strand between them. A residue on this intervening strand, M236, appears to transmit fine structural perturbations to the catalytic metal-coordinating residue D256, affecting its conformational stability.

PubMed: 28402631
DOI: 10.1021/acs.biochem.6b01287

Experimental method

X-RAY DIFFRACTION (2.155 Å)