1EA6

N-terminal 40kDa fragment of NhPMS2 complexed with ADP

Summary for 1EA6

• Entry DOI: 10.2210/pdb1ea6/pdb
• Related: 1H7S 1H7U
• Descriptor: PMS1 PROTEIN HOMOLOG 2, MAGNESIUM ION, ADENOSINE-5'-DIPHOSPHATE, ... (4 entities in total)
• Functional Keywords: dna repair, ghl atpase, hnpcc, mismatch repair
• Biological source: HOMO SAPIENS (HUMAN)
• Total number of polymer chains: 2
• Total formula weight: 81755.32

Authors

Guarne, A.,Junop, M.S.,Yang, W. (deposition date: 2001-07-10, release date: 2001-11-23, Last modification date: 2024-10-23)

Primary citation

Guarne, A.,Junop, M.S.,Yang, W.
Structure and Function of the N-Terminal 40 kDa Fragment of Human Pms2: A Monomeric Ghl ATPase
Embo J., 20:5521-, 2001

PubMed Abstract: Human MutLalpha, a heterodimer of hMLH1 and hPMS2, is essential for DNA mismatch repair. Inactivation of the hmlh1 or hpms2 genes by mutation or epigenesis causes genomic instability and a predisposition to hereditary non-polyposis cancer. We report here the X-ray crystal structures of the conserved N-terminal 40 kDa fragment of hPMS2, NhPMS2, and its complexes with ATPgammaS and ADP at 1.95, 2.7 and 2.7 A resolution, respectively. The NhPMS2 structures closely resemble the ATPase fragment of Escherichia coli MutL, which coordinates protein-protein interactions in mismatch repair by undergoing structural transformation upon binding of ATP. Unlike the E.coli MutL, whose ATPase activity requires protein dimerization, the monomeric form of NhPMS2 is active both in ATP hydrolysis and DNA binding. NhPMS2 is the first example of a GHL ATPase active as a monomer, suggesting that its activity may be modulated by hMLH1 in MutLalpha, and vice versa. The potential heterodimer interface revealed by crystallography provides a mutagenesis target for functional studies of MutLalpha.

PubMed: 11574484
DOI: 10.1093/EMBOJ/20.19.5521

Experimental method

X-RAY DIFFRACTION (2.7 Å)