title: Crystal structure of a transition state mimic of the catalytic subunit of cAMP-dependent protein kinase.
abstract: To understand the molecular mechanism underlying phosphoryl transfer of cAMP-dependent protein kinase, the structure of the catalytic subunit in complex with ADP, aluminum fluoride, Mg2+ ions and a substrate peptide was determined at 2.0 A resolution. Aluminum fluoride was modeled as AlF3 in a planar geometry; it is positioned 2.3 A from both the donor oxygen of ADP and the hydroxyl group of the recipient Ser residue. In this configuration, the aluminum atom forms a trigonal bipyramidal coordination with the oxygen atoms of the donor and recipient groups at the apical positions. This arrangement suggests that aluminum fluoride mimics the transition state and provides the first direct structural evidence for the in-line mechanism of phosphoryl transfer in a protein kinase.
authors.affiliation: Department of Chemistry & Biochemistry, University of California, San Diego, La Jolla, California 92093-0654, USA.
authors.lastname: Madhusudan
authors.forename: Pearl
authors.initials: P
authors.lastname: Akamine
authors.forename: Nguyen-Huu
authors.initials: NH
authors.lastname: Xuong
authors.forename: Susan S
authors.initials: SS
authors.lastname: Taylor
mesh_terms: D000244:Adenosine Diphosphate / Q000378:metabolism; D017607:Aluminum Compounds / Q000378:metabolism; D000818:Animals; D001665:Binding Sites; D020134:Catalytic Domain; D018360:Crystallography, X-Ray; D017868:Cyclic AMP-Dependent Protein Kinases / Q000737:chemistry* / Q000378:metabolism*; D005459:Fluorides / Q000378:metabolism; D006860:Hydrogen Bonding; D008274:Magnesium / Q000378:metabolism; D051379:Mice; D008958:Models, Molecular; D018716:Molecular Mimicry; D011487:Protein Conformation; D021122:Protein Subunits; D013329:Structure-Activity Relationship
chemical_list: D017607:Aluminum Compounds; D021122:Protein Subunits; D000244:Adenosine Diphosphate; D017868:Cyclic AMP-Dependent Protein Kinases; D008274:Magnesium; D005459:Fluorides; C032311:aluminum fluoride