3TQ1

Human DNA Polymerase eta in binary complex with DNA

Summary for 3TQ1

• Entry DOI: 10.2210/pdb3tq1/pdb
• Descriptor: DNA polymerase eta, DNA (5'-D(*TP*CP*AP*TP*TP*AP*TP*GP*AP*CP*GP*CP*T)-3'), DNA (5'-D(*TP*AP*GP*CP*GP*TP*CP*AP*T)-3'), ... (4 entities in total)
• Functional Keywords: polymerase, dna replication, transferase-dna complex, transferase/dna
• Biological source: Homo sapiens (human); More
• Cellular location: Nucleus: Q9Y253
• Total number of polymer chains: 3
• Total formula weight: 55318.16

Authors

Ummat, A.,Silverstein, T.D.,Jain, R.,Buku, A.,Johnson, R.E.,Prakash, L.,Prakash, S.,Aggarwal, A.K. (deposition date: 2011-09-08, release date: 2012-02-08, Last modification date: 2024-02-28)

Primary citation

Ummat, A.,Silverstein, T.D.,Jain, R.,Buku, A.,Johnson, R.E.,Prakash, L.,Prakash, S.,Aggarwal, A.K.
Human DNA Polymerase Eta Is Pre-Aligned for dNTP Binding and Catalysis.
J.Mol.Biol., 415:627-634, 2012

PubMed Abstract: Pre-steady-state kinetic studies on Y-family DNA polymerase η (Polη) have suggested that the polymerase undergoes a rate-limiting conformational change step before the phosphoryl transfer of the incoming nucleotide to the primer terminus. However, the nature of this rate-limiting conformational change step has been unclear, due in part to the lack of structural information on the Polη binary complex. We present here for the first time a crystal structure of human Polη (hPolη) in binary complex with its DNA substrate. We show that the hPolη domains move only slightly on dNTP binding and that the polymerase by and large is pre-aligned for dNTP binding and catalysis. We also show that there is no major reorientation of the DNA from a nonproductive to a productive configuration and that the active site is devoid of metals in the absence of dNTP. Together, these observations lead us to suggest that the rate-limiting conformational change step in the Polη replication cycle likely corresponds to a rate-limiting entry of catalytic metals in the active site.

PubMed: 22154937
DOI: 10.1016/j.jmb.2011.11.038

Experimental method

X-RAY DIFFRACTION (2.556 Å)