PDBsum entry 1tva

Transferase/DNA

PDB id: 1tva

Contents

Protein chain

331 a.a. *

DNA/RNA

Ligands

PO4

Metals

_MG ×2

_NA ×2

Waters ×225

* Residue conservation analysis

PDB id:

1tva

Name:

Transferase/DNA

Title:

Human DNA polymerase beta complexed with nicked DNA containing a mismatched template thymidine and incoming cytidine

Structure:

5'-d( Cp Cp Gp Ap Cp Tp Gp Cp Gp Cp Ap Tp Cp Ap Gp C)-3'. Chain: t. Engineered: yes. 5'-d( Gp Cp Tp Gp Ap Tp Gp Cp Gp Cp C)-3'. Chain: p. Engineered: yes. 5'-d(p Gp Tp Cp Gp G)-3'. Chain: d. Engineered: yes.

Source:

Synthetic: yes. Homo sapiens. Human. Organism_taxid: 9606. Gene: polb. Expressed in: escherichia coli. Expression_system_taxid: 562

Biol. unit:

Tetramer (from PQS)

Resolution:

2.60Å R-factor: 0.212 R-free: 0.282

Authors:

J.M.Krahn,W.A.Beard,S.H.Wilson

Key ref:

J.M.Krahn et al. (2004). Structural insights into DNA polymerase beta deterrents for misincorporation support an induced-fit mechanism for fidelity. Structure, 12, 1823-1832. PubMed id: 15458631 DOI: 10.1016/j.str.2004.08.001

Date:

29-Jun-04 Release date: 23-Nov-04

Protein chain

P06746  (DPOLB_HUMAN) -  DNA polymerase beta from Homo sapiens

Seq: 335 a.a.

Struc: 331 a.a.

DNA/RNA chains

C-C-G-A-C-T-G-C-G-C-A-T-C-A-G-C 16 bases

G-C-T-G-A-T-G-C-G-C-C 11 bases

G-T-C-G-G 5 bases

Enzyme reactions

• Enzyme class 1: E.C.2.7.7.7 - DNA-directed Dna polymerase.
• Reaction: DNA(n) + a 2'-deoxyribonucleoside 5'-triphosphate = DNA(n+1) + diphosphate

DNA(n) + 2'-deoxyribonucleoside 5'-triphosphate = DNA(n+1) (Bound ligand (Het Group name = PO4) matches with 55.56% similarity) + diphosphate

• Enzyme class 2: E.C.4.2.99.- - ?????
• Enzyme class 3: E.C.4.2.99.18 - DNA-(apurinic or apyrimidinic site) lyase.
• Reaction: 2'-deoxyribonucleotide-(2'-deoxyribose 5'-phosphate)- 2'-deoxyribonucleotide-DNA = a 3'-end 2'-deoxyribonucleotide-(2,3- dehydro-2,3-deoxyribose 5'-phosphate)-DNA + a 5'-end 5'-phospho- 2'-deoxyribonucleoside-DNA + H⁺

Note, where more than one E.C. class is given (as above), each may correspond to a different protein domain or, in the case of polyprotein precursors, to a different mature protein.

Molecule diagrams generated from .mol files obtained from the KEGG ftp site

Added reference

DOI no: 10.1016/j.str.2004.08.001

Structure 12:1823-1832 (2004)

PubMed id: 15458631

Structural insights into DNA polymerase beta deterrents for misincorporation support an induced-fit mechanism for fidelity.

J.M.Krahn, W.A.Beard, S.H.Wilson.

ABSTRACT

DNA polymerases generally select the correct nucleotide from a pool of structurally similar molecules to preserve Watson-Crick base-pairing rules. We report the structure of DNA polymerase beta with DNA mismatches situated in the polymerase active site. This was achieved by using nicked product DNA that traps the mispair (template-primer, A-C or T-C) in the nascent base pair binding pocket. The structure of each mispair complex indicates that the bases do not form hydrogen bonds with one another, but form a staggered arrangement where the bases of the mispair partially overlap. This prevents closure/opening of the N subdomain that is believed to be required for catalytic cycling. The partially open conformation of the N subdomain results in distinct hydrogen bonding networks that are unique for each mispair. These structures define diverse molecular aspects of misinsertion that are consistent with the induced-fit model for substrate specificity.

Selected figure(s)

Figure 6.
Figure 6. Comparison of Alternate DNA and N-Subdomain ConformationsThe conformation of the N subdomain, as monitored by the position of a helix N, for the NAC mismatch structure (green) is in an intermediate position relative to the active closed (blue; Protein Data Bank entry 1BPY) or inactive open (red; Protein Data Bank entry 1BPX) conformations. These structures were superimposed using the C subdomains. The template strand is displaced to a greater extent than that observed for the open binary DNA complex relative to the closed ternary complex. The position of a helix N and the template strand in the open nicked complex (not shown; Protein Data Bank entry 1BPZ) is identical to that illustrated for the open complex.

The above figure is reprinted by permission from Cell Press: Structure (2004, 12, 1823-1832) copyright 2004.

Figure was selected by the author.