PDBsum entry 4o3m

Hydrolase/DNA

PDB id: 4o3m

Contents

Protein chain

613 a.a.

DNA/RNA

Ligands

ADP

EDO ×8

Metals

_CA

_ZN

Waters ×60

PDB id:

4o3m

Name:

Hydrolase/DNA

Title:

Ternary complex of bloom's syndrome helicase

Structure:

Bloom syndrome protein. Chain: a. Synonym: DNA helicase, recq-like type 2, recq2, recq protein-like 3. Engineered: yes. 5'-d( Ap Gp Cp Gp Tp Cp Gp Ap Gp Ap Tp Cp Cp Ap Ap G)-3'. Chain: p. Engineered: yes. 5'-d( Cp Tp Tp Gp Gp Ap Tp Cp Tp Cp Gp Ap Cp Gp Cp Tp Cp Tp Cp Cp Cp Tp Tp A)-3'.

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: blm, recq2, recql3. Expressed in: escherichia coli. Expression_system_taxid: 562. Synthetic: yes. Other_details: chemically synthesised oligonucleotide.. Other_details: chemically synthesised oligonucleotide.

Resolution:

2.30Å R-factor: 0.183 R-free: 0.215

Authors:

M.K.Swan,J.Bertrand

Key ref:

M.K.Swan et al. (2014). Structure of human Bloom's syndrome helicase in complex with ADP and duplex DNA. Acta Crystallogr D Biol Crystallogr, 70, 1465-1475. PubMed id: 24816114 DOI: 10.1107/S139900471400501X

Date:

18-Dec-13 Release date: 12-Mar-14

Protein chain

P54132  (BLM_HUMAN) -  RecQ-like DNA helicase BLM from Homo sapiens

Seq: 1417 a.a.

Struc: 613 a.a.

DNA/RNA chains

G-C-G-T-C-G-A-G-A-T-C-C 12 bases

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

Enzyme reactions

• Enzyme class: E.C.3.6.4.12 - Dna helicase.
• Reaction: ATP + H2O = ADP + phosphate + H⁺

ATP + H2O = ADP (Bound ligand (Het Group name = ADP) corresponds exactly) + phosphate + H(+)

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

reference

DOI no: 10.1107/S139900471400501X

Acta Crystallogr D Biol Crystallogr 70:1465-1475 (2014)

PubMed id: 24816114

Structure of human Bloom's syndrome helicase in complex with ADP and duplex DNA.

M.K.Swan, V.Legris, A.Tanner, P.M.Reaper, S.Vial, R.Bordas, J.R.Pollard, P.A.Charlton, J.M.Golec, J.A.Bertrand.

ABSTRACT

Bloom's syndrome is an autosomal recessive genome-instability disorder associated with a predisposition to cancer, premature aging and developmental abnormalities. It is caused by mutations that inactivate the DNA helicase activity of the BLM protein or nullify protein expression. The BLM helicase has been implicated in the alternative lengthening of telomeres (ALT) pathway, which is essential for the limitless replication of some cancer cells. This pathway is used by 10-15% of cancers, where inhibitors of BLM are expected to facilitate telomere shortening, leading to apoptosis or senescence. Here, the crystal structure of the human BLM helicase in complex with ADP and a 3'-overhang DNA duplex is reported. In addition to the helicase core, the BLM construct used for crystallization (residues 640-1298) includes the RecQ C-terminal (RQC) and the helicase and ribonuclease D C-terminal (HRDC) domains. Analysis of the structure provides detailed information on the interactions of the protein with DNA and helps to explain the mechanism coupling ATP hydrolysis and DNA unwinding. In addition, mapping of the missense mutations onto the structure provides insights into the molecular basis of Bloom's syndrome.