PDBsum entry 1nzp

DNA binding protein/transferase

PDB id: 1nzp

Contents

Protein chain

86 a.a. *

* Residue conservation analysis

PDB id:

1nzp

Name:

DNA binding protein/transferase

Title:

Solution structure of the lyase domain of human DNA polymerase lambda

Structure:

DNA polymerase lambda. Chain: a. Fragment: polymerase lambda lyase domain(residues 242 - 327). Synonym: pol lambda, DNA polymerase lambda, DNA polymerase beta-2, pol beta2. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: poll. Expressed in: escherichia coli. Expression_system_taxid: 562.

NMR struc:

8 models

Authors:

E.F.Derose,T.W.Kirby,G.A.Mueller,K.Bebenek,M.Garcia-Diaz,L.Blanco, T.A.Kunkel,R.E.London

Key ref:

E.F.DeRose et al. (2003). Solution structure of the lyase domain of human DNA polymerase lambda. Biochemistry, 42, 9564-9574. PubMed id: 12911298 DOI: 10.1021/bi034298s

Date:

19-Feb-03 Release date: 05-Aug-03

Protein chain

Q9UGP5  (DPOLL_HUMAN) -  DNA polymerase lambda from Homo sapiens

Seq: 575 a.a.

Struc: 86 a.a.

Enzyme reactions

• Enzyme class 2: E.C.2.7.7.7 - DNA-directed Dna polymerase.
• Reaction: DNA(n) + a 2'-deoxyribonucleoside 5'-triphosphate = DNA(n+1) + diphosphate
• Enzyme class 3: E.C.4.2.99.- - ?????

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: 10.1021/bi034298s

Biochemistry 42:9564-9574 (2003)

PubMed id: 12911298

Solution structure of the lyase domain of human DNA polymerase lambda.

E.F.DeRose, T.W.Kirby, G.A.Mueller, K.Bebenek, M.Garcia-Diaz, L.Blanco, T.A.Kunkel, R.E.London.

ABSTRACT

DNA polymerase lambda (pol lambda) is a recently discovered nuclear enzyme belonging to the pol X family of DNA polymerases that exhibits a 32% sequence identity with the nuclear DNA repair protein, pol beta. Structural modeling suggests that pol lambda contains the palm, fingers, thumb, and 8 kDa lyase domains present in pol beta, as well as an additional N-terminal BRCT domain and a serine-proline-rich linker that are presumably involved in protein-protein interactions. The 8 kDa domain of pol beta is important for DNA binding and contains the dRP lyase activity, which is the rate-limiting step in the single-nucleotide base excision repair (BER) pathway of damaged DNA. Recently, it was shown that the 8 kDa domain of pol lambda also contains the dRP lyase activity. To gain further insight into the catalytic mechanism of dRP removal by pol lambda, we have determined the solution structure of the 8 kDa lyase domain of human DNA pol lambda via multidimensional NMR methods and the ARIA program. The resulting structures exhibited a high degree of similarity with the 8 kDa lyase domain of pol beta. Specifically, the side chains of residues W274, R275, Y279, K307, R308, and K312 are in similar positions to the functionally important side chains of residues H34, K35, Y39, K60, K68, and K72 in the 8 kDa lyase domain of pol beta. This suggests that, on the basis of the proposed roles of these residues in pol beta, the corresponding pol lambda side chains may be involved in DNA binding and dRP lyase activity. The structural alignment of W274 (pol lambda) with H34 (pol beta) indicates that the former is probably involved in a similar base stacking interaction with template DNA at the position of the gap, in contrast with several previous proposals which aligned D272 with H34. In a few cases for which there is a nonconservative substitution in the sequence alignment, a structural comparison shows a positionally and, hence, probably a functionally equivalent residue, e.g., K60 in pol beta and K307 in pol lambda. Additionally, on the basis of the structural alignment obtained, several previously proposed mechanistic hypotheses can be evaluated.