Statistical coevolution analysis and molecular dynamics: Identification of amino acid pairs essential for catalysis
AUTOR(ES)
Estabrook, R. August
FONTE
National Academy of Sciences
RESUMO
Molecular dynamics (MD) simulations of HhaI DNA methyltransferase and statistical coupling analysis (SCA) data on the DNA cytosine methyltransferase family were combined to identify residues that are coupled by coevolution and motion. The highest ranking correlated pairs from the data matrix product (SCA·MD) are colocalized and form stabilizing interactions; the anticorrelated pairs are separated on average by 30 Å and form a clear focal point centered near the active site. We suggest that these distal anti-correlated pairs are involved in mediating active-site compressions that may be important for catalysis. Mutants that disrupt the implicated interactions support the validity of our combined SCA·MD approach.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=545822Documentos Relacionados
- Gradient pattern analysis of structural dynamics: application to molecular system relaxation
- Identification of residues in the Mu transposase essential for catalysis.
- Identification of Amino Acid Residues of Influenza Virus Nucleoprotein Essential for RNA Binding
- Identification of amino acid residues essential for the enzymatic activities of pertussis toxin.
- Inducible nitric oxide synthase: identification of amino acid residues essential for dimerization and binding of tetrahydrobiopterin.