1NNE

Crystal Structure of the MutS-ADPBeF3-DNA complex

Summary for 1NNE

• Entry DOI: 10.2210/pdb1nne/pdb
• Related: 1EWQ 1EWR 1FW6
• Descriptor: 5'-D(*GP*CP*GP*AP*CP*GP*CP*TP*AP*GP*CP*GP*TP*GP*CP*GP*GP*CP*TP*CP*GP*TP*C)-3', 5'-D(P*GP*GP*AP*CP*GP*AP*GP*CP*CP*GP*CP*CP*GP*CP*TP*AP*GP*CP*GP*TP*CP*G)-3', DNA Mismatch Repair protein MutS, ... (8 entities in total)
• Functional Keywords: dna, dna binding protein-dna complex, dna binding protein/dna
• Biological source: Thermus aquaticus
• Total number of polymer chains: 4
• Total formula weight: 186647.45

Authors

Alani, E.,Lee, J.Y.,Schofield, M.J.,Kijas, A.W.,Hsieh, P.,Yang, W. (deposition date: 2003-01-13, release date: 2003-05-20, Last modification date: 2024-02-14)

Primary citation

Alani, E.,Lee, J.Y.,Schofield, M.J.,Kijas, A.W.,Hsieh, P.,Yang, W.
Crystal structure and biochemical analysis of the MutS-ADP-Beryllium Fluoride complex suggests a conserved mechanism for ATP interactions in mismatch repair
J.Biol.Chem., 278:16088-16094, 2003

PubMed Abstract: During mismatch repair ATP binding and hydrolysis activities by the MutS family proteins are important for both mismatch recognition and for transducing mismatch recognition signals to downstream repair factors. Despite intensive efforts, a MutS.ATP.DNA complex has eluded crystallographic analysis. Searching for ATP analogs that strongly bound to Thermus aquaticus (Taq) MutS, we found that ADP.beryllium fluoride (ABF), acted as a strong inhibitor of several MutS family ATPases. Furthermore, ABF promoted the formation of a ternary complex containing the Saccharomyces cerevisiae MSH2.MSH6 and MLH1.PMS1 proteins bound to mismatch DNA but did not promote dissociation of MSH2.MSH6 from mismatch DNA. Crystallographic analysis of the Taq MutS.DNA.ABF complex indicated that although this complex was very similar to that of MutS.DNA.ADP, both ADP.Mg(2+) moieties in the MutS. DNA.ADP structure were replaced by ABF. Furthermore, a disordered region near the ATP-binding pocket in the MutS B subunit became traceable, whereas the equivalent region in the A subunit that interacts with the mismatched nucleotide remained disordered. Finally, the DNA binding domains of MutS together with the mismatched DNA were shifted upon binding of ABF. We hypothesize that the presence of ABF is communicated between the two MutS subunits through the contact between the ordered loop and Domain III in addition to the intra-subunit helical lever arm that links the ATPase and DNA binding domains.

PubMed: 12582174
DOI: 10.1074/jbc.M213193200

Experimental method

X-RAY DIFFRACTION (3.11 Å)