PDBsum entry 3l2p

Ligase/DNA

PDB id: 3l2p

Contents

Protein chain

535 a.a. *

DNA/RNA

Ligands

AMP

* Residue conservation analysis

PDB id:

3l2p

Name:

Ligase/DNA

Title:

Human DNA ligase iii recognizes DNA ends by dynamic switching between two DNA bound states

Structure:

DNA ligase 3. Chain: a. Fragment: unp residues 257-833. Synonym: DNA ligase iii, polydeoxyribonucleotide synthase [atp] 3. Engineered: yes. 5'-d(p Cp Gp Gp Gp Ap Tp Gp Cp Gp Tp C)-3'. Chain: b. Engineered: yes. 5'-d( Gp Tp Cp Gp Gp Ap Cp Tp G)-3'.

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: lig3. Expressed in: escherichia coli. Expression_system_taxid: 562. Synthetic: yes. Other_details: synthetic construct. Other_details: synthetic construct

Resolution:

3.00Å R-factor: 0.235 R-free: 0.271

Authors:

E.A.Cotner-Gohara,I.K.Kim,M.Hammel,J.A.Tainer,A.Tomkinson, T.Ellenberger

Key ref:

E.Cotner-Gohara et al. (2010). Human DNA ligase III recognizes DNA ends by dynamic switching between two DNA-bound states. Biochemistry, 49, 6165-6176. PubMed id: 20518483

Date:

15-Dec-09 Release date: 14-Jul-10

Protein chain

P49916  (DNLI3_HUMAN) -  DNA ligase 3 from Homo sapiens

Seq: 1009 a.a.

Struc: 535 a.a.*

* PDB and UniProt seqs differ at 2 residue positions (black crosses)

DNA/RNA chains

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

G-T-C-G-G-A-C-T-G 9 bases

G-C-C-A-G-T-C-C-G-A-C-G-A-C-G-C-A-T-C-C-C-G 22 bases

Enzyme reactions

• Enzyme class: E.C.6.5.1.1 - Dna ligase (ATP).
• Reaction: ATP + (deoxyribonucleotide)n-3'-hydroxyl + 5'-phospho- (deoxyribonucleotide)m = (deoxyribonucleotide)n+m + AMP + diphosphate

ATP + (deoxyribonucleotide)n-3'-hydroxyl + 5'-phospho- (deoxyribonucleotide)m = (deoxyribonucleotide)n+m + AMP (Bound ligand (Het Group name = AMP) matches with 95.65% similarity) + diphosphate

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

reference

Biochemistry 49:6165-6176 (2010)

PubMed id: 20518483

Human DNA ligase III recognizes DNA ends by dynamic switching between two DNA-bound states.

E.Cotner-Gohara, I.K.Kim, M.Hammel, J.A.Tainer, A.E.Tomkinson, T.Ellenberger.

ABSTRACT

Human DNA ligase III has essential functions in nuclear and mitochondrial DNA replication and repair and contains a PARP-like zinc finger (ZnF) that increases DNA nick-joining and intermolecular DNA ligation. Yet, the bases for ligase III specificity and structural variation among human ligases are not understood. Here combined crystal structure and small angle x-ray scattering results reveal dynamic switching between two nick-binding components of ligase III: the ZnF-DNA binding domain (DBD) form a crescent-shaped surface used for DNA end recognition which switches to a ring formed by the nucleotidyl transferase (NTase) -OB-fold (OBD) domains for catalysis. Structural and mutational analyses indicate that high flexibility and distinct DNA binding domain features in ligase III assist both nick-sensing and the transition from nick-sensing by the ZnF to nick-joining by the catalytic core. The collective results support a "jackknife model" whereby the ZnF loads ligase III onto nicked DNA and conformational changes deliver DNA into the active site. This work has implications for the biological specificity of DNA ligases and functions of PARP-like zinc fingers.