1nne
From Proteopedia
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'''Crystal Structure of the MutS-ADPBeF3-DNA complex''' | '''Crystal Structure of the MutS-ADPBeF3-DNA complex''' | ||
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[[Category: Schofield, M J.]] | [[Category: Schofield, M J.]] | ||
[[Category: Yang, W.]] | [[Category: Yang, W.]] | ||
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Revision as of 23:44, 2 May 2008
Crystal Structure of the MutS-ADPBeF3-DNA complex
Overview
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.
About this Structure
1NNE is a Single protein structure of sequence from Thermus aquaticus. Full crystallographic information is available from OCA.
Reference
Crystal structure and biochemical analysis of the MutS.ADP.beryllium fluoride complex suggests a conserved mechanism for ATP interactions in mismatch repair., Alani E, Lee JY, Schofield MJ, Kijas AW, Hsieh P, Yang W, J Biol Chem. 2003 May 2;278(18):16088-94. Epub 2003 Feb 11. PMID:12582174 Page seeded by OCA on Sat May 3 02:44:45 2008
