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Site‐directed mutagenesis and structural modeling of Coq10p indicate the presence of a tunnel for coenzyme Q6 binding
Author(s) -
Busso Cleverson,
Bleicher Lucas,
Ferreira-Júnior José Ribamar,
Barros Mario H.
Publication year - 2010
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2010.03.024
Subject(s) - mutagenesis , site directed mutagenesis , point mutation , superfamily , molecular model , function (biology) , directed mutagenesis , binding site , cofactor , protein structure , computational biology , biology , chemistry , biochemistry , mutation , genetics , biophysics , gene , mutant , enzyme
Coq10p is a protein required for coenzyme Q function, but its specific role is still unknown. It is a member of the START domain superfamily that contains a hydrophobic tunnel implicated in the binding of lipophilic molecules. We used site‐directed mutagenesis, statistical coupling analysis and molecular modeling to probe structural determinants in the Coq10p putative tunnel. Four point mutations were generated ( coq10‐K50E , coq10‐L96S , coq10‐E105K and coq10‐K162D ) and their biochemical properties analysed, as well as structural consequences. Our results show that all mutations impaired Coq10p function and together with molecular modeling indicate an important role for the Coq10p putative tunnel.