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Crystal structure and functional analysis identify the P‐loop containing protein YFH7 of Saccharomyces cerevisiae as an ATP‐dependent kinase
Author(s) -
GueguenChaig Virginie,
Chaptal Vincent,
Larivière Laurent,
Costa Narciso,
Lopes Philippe,
Morera Solange,
Nessler Sylvie
Publication year - 2007
Publication title -
proteins: structure, function, and bioinformatics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.699
H-Index - 191
eISSN - 1097-0134
pISSN - 0887-3585
DOI - 10.1002/prot.21740
Subject(s) - saccharomyces cerevisiae , biochemistry , biology , yeast , subfamily , protein kinase domain , kinase , structural similarity , sequence alignment , function (biology) , peptide sequence , computational biology , genetics , gene , mutant
Genome sequencing projects have revealed that P‐loop proteins are highly represented in all organisms and that many of them have no attributed function. They are characterized by a conserved nucleotide‐binding domain and carry different activities implicated in many cellular processes. Saccharomyces cerevisiae YFH7 is one of these P‐loop proteins of unknown function. In this work we tried to integrate bioinformatics, structure, and enzymology to discover the function of YFH7. Sequence analysis revealed that yeast YFH7 is a yeast‐specific protein showing weak similarity with the phosphoribulokinase/uridine kinase/bacterial pantothenate kinase (PRK/URK/PANK) subfamily of P‐loop containing kinases. A large insertion of about 100 residues distinguishes YFH7 from other members of the family. The 1.95 Å resolution crystal structure of YFH7 solved using the SAD method confirmed that YFH7 has a fold similar to the PRK/URK/PANK family, with the characteristic core, lid, and NMP bind domains. An additional α/β domain of novel topology corresponds to the large sequence insertion. Structural and ligand binding analysis combined with enzymatic assays suggest that YFH7 is an ATP‐dependent small molecule kinase with new substrate specificity. Proteins 2008. © 2007 Wiley‐Liss, Inc.