An incoming nucleotide imposes an anti to syn conformational change on the templating purine in the human DNA polymerase-iota active site

Structure
Deepak T NairAneel K Aggarwal

Abstract

Substrate-induced conformational change of the protein is the linchpin of enzymatic reactions. Replicative DNA polymerases, for example, convert from an open to a closed conformation in response to dNTP binding. Human DNA polymerase-iota (hPoliota), a member of the Y family of DNA polymerases, differs strikingly from other polymerases in its much higher proficiency and fidelity for nucleotide incorporation opposite template purines than opposite template pyrimidines. We present here a crystallographic analysis of hPoliota binary complexes, which together with the ternary complexes show that, contrary to replicative DNA polymerases, the DNA, and not the polymerase, undergoes the primary substrate-induced conformational change. The incoming dNTP "pushes" templates A and G from the anti to the syn conformation dictated by a rigid hPoliota active site. Together, the structures posit a mechanism for template selection wherein dNTP binding induces a conformational switch in template purines for productive Hoogsteen base pairing.

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Citations

Aug 19, 2007·Molecular and Cellular Biology·Robert E JohnsonLouise Prakash
Nov 6, 2008·The Journal of Biological Chemistry·Matthew G PenceFred W Perrino
Oct 14, 2009·Proceedings of the National Academy of Sciences of the United States of America·Jung-Hoon YoonSatya Prakash
Oct 22, 2010·The Journal of Biological Chemistry·Matthew G PenceF Peter Guengerich
Feb 9, 2011·Proceedings of the National Academy of Sciences of the United States of America·Kevin N Kirouac, Hong Ling
Apr 16, 2009·Cellular and Molecular Life Sciences : CMLS·Caixia GuoErrol C Friedberg
Dec 14, 2011·Journal of Molecular Biology·Ajay UmmatAneel K Aggarwal
Apr 13, 2011·Current Opinion in Structural Biology·Karl E ZahnSylvie Doublié
Feb 4, 2010·Biochimica Et Biophysica Acta·Janice D Pata
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May 26, 2009·Journal of Molecular Biology·Michael K SwanAneel K Aggarwal
Jul 15, 2015·IUBMB Life·Deepak T NairRahul Sharma
Mar 1, 2011·Journal of Molecular Biology·Rodrigo Vasquez-Del CarpioAneel K Aggarwal
Feb 16, 2008·Structure·Patrick Sung
Jul 17, 2009·Structure·Rinku JainAneel K Aggarwal
Apr 17, 2009·Structure·Deepak T NairAneel K Aggarwal
Mar 11, 2017·Critical Reviews in Biochemistry and Molecular Biology·Alexandra Vaisman, Roger Woodgate
Mar 2, 2018·Annual Review of Biochemistry·Wei Yang, Yang Gao
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Dec 15, 2017·The Journal of Physical Chemistry Letters·Debayan Chakraborty, David J Wales

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