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Science 24 June 1994:
Vol. 264. no. 5167, pp. 1930 - 1935
DOI: 10.1126/science.7516581
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Articles

Science, Vol 264, Issue 5167, 1930-1935
Copyright © 1994 by American Association for the Advancement of Science

articles

Crystal structure of rat DNA polymerase beta: evidence for a common polymerase mechanism

MR Sawaya, H Pelletier, A Kumar, SH Wilson, and J Kraut

Department of Chemistry, University of California, San Diego 92093-0317.

Structures of the 31-kilodalton catalytic domain of rat DNA polymerase beta (pol beta) and the whole 39-kilodalton enzyme were determined at 2.3 and 3.6 angstrom resolution, respectively. The 31-kilodalton domain is composed of fingers, palm, and thumb subdomains arranged to form a DNA binding channel reminiscent of the polymerase domains of the Klenow fragment of Escherichia coli DNA polymerase I, HIV-1 reverse transcriptase, and bacteriophage T7 RNA polymerase. The amino-terminal 8-kilodalton domain is attached to the fingers subdomain by a flexible hinge. The two invariant aspartates found in all polymerase sequences and implicated in catalytic activity have the same geometric arrangement within structurally similar but topologically distinct palms, indicating that the polymerases have maintained, or possibly re-evolved, a common nucleotidyl transfer mechanism. The location of Mn2+ and deoxyadenosine triphosphate in pol beta confirms the role of the invariant aspartates in metal ion and deoxynucleoside triphosphate binding.


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