Thrombin: a paradigm for enzymes allosterically activated by monovalent cations.
Enzymes activated by monovalent cations are abundantly represented in plants and in the animal world. The mechanism, of activation involves formation of a ternary intermediate with the enzyme-substrate complex, or binding of the cation to an allosteric site in the protein. Thrombin is a Na+-activated enzyme with procoagulant, anticoagulant and signaling roles. The binding of Na+ influences allosterically thrombin function and offers a paradigm for regulatory control of protease activity and specificity. Here we review the molecular basis of thrombin allostery as recently emerged from mutagenesis and structural studies. The role of Na+ in blood coagulation and the evolution of serine proteases are also discussed.
Di Cera
Enrico
E
Department of Biochemistry and Molecular Biophysics, Washington University School of Medicine, St Louis, MO 63110, USA. enrico@wustl.edu
D000495:Allosteric Site; D001777:Blood Coagulation / Q000502:physiology; D002414:Cations, Monovalent / Q000378:metabolism*; D019143:Evolution, Molecular; D017434:Protein Structure, Tertiary; D012697:Serine Endopeptidases; D012964:Sodium / Q000502:physiology; D013917:Thrombin / Q000502:physiology*
D002414:Cations, Monovalent; D012964:Sodium; D012697:Serine Endopeptidases; D013917:Thrombin