Analyzing the binding of Co(II)-specific inhibitors to the methionyl aminopeptidases from Escherichia coli and Pyrococcus furiosus. J Biol Inorg Chem 2009 May;14(4):573-85
Date
02/10/2009Pubmed ID
19198897Pubmed Central ID
PMC2678238DOI
10.1007/s00775-009-0471-2Scopus ID
2-s2.0-67349143658 (requires institutional sign-in at Scopus site) 8 CitationsAbstract
Methionine aminopeptidases (MetAPs) represent a unique class of protease that is capable of the hydrolytic removal of an N-terminal methionine residue from nascent polypeptide chains. MetAPs are physiologically important enzymes; hence, there is considerable interest in developing inhibitors that can be used as antiangiogenic and antimicrobial agents. A detailed kinetic and spectroscopic study has been performed to probe the binding of a triazole-based inhibitor and a bestatin-based inhibitor to both Mn(II)- and Co(II)-loaded type-I (Escherichia coli) and type-II (Pyrococcus furiosus) MetAPs. Both inhibitors were found to be moderate competitive inhibitors. The triazole-type inhibitor was found to interact with both active-site metal ions, while the bestatin-type inhibitor was capable of switching its mode of binding depending on the metal in the active site and the type of MetAP enzyme.
Author List
Mitra S, Sheppard G, Wang J, Bennett B, Holz RCAuthor
Brian Bennett D.Phil. Professor and Chair in the Physics department at Marquette UniversityMESH terms used to index this publication - Major topics in bold
AminopeptidasesBinding Sites
Catalytic Domain
Cobalt
Enzyme Inhibitors
Escherichia coli
Escherichia coli Proteins
Leucine
Manganese
Methionyl Aminopeptidases
Molecular Structure
Protein Binding
Pyrococcus furiosus
Thermodynamics
Triazoles
