Intra- and interdomain flexibility in matrix metalloproteinases: functional aspects and drug design.
Matrix metalloproteinases are involved in many biological processes and in a large set of diseases. In the last twenty years the genetics, functions, and the structural features of this family of proteolytic enzymes have been investigated and a large number of synthetic inhibitors designed and tested. A better knowledge of the dynamical features of these proteins can be relevant not only to reveal new biological activities but also to design more specific and selective inhibitors. Here, we report the common and the distinct structural features of these proteins, the most recent published information on protein dynamics in matrix metalloproteinases and the recent results on the catalytic mechanism. The implications of the observed intra- and interdomain flexibility in matrix metalloproteinases for drug design have been analyzed and discussed.
Bertini
Ivano
I
Magnetic Resonance Center (CERM), University of Florence, Via L. Sacconi 6, 50019 Sesto Fiorentino, Italy. ivanobertini@cerm.unifi.it
Fragai
Marco
M
Luchinat
Claudio
C
D002384:Catalysis; D020134:Catalytic Domain; D015195:Drug Design; D006801:Humans; D061965:Matrix Metalloproteinase Inhibitors; D020782:Matrix Metalloproteinases / Q000737:chemistry / Q000378:metabolism*; D011480:Protease Inhibitors / Q000494:pharmacology*; D011487:Protein Conformation
D061965:Matrix Metalloproteinase Inhibitors; D011480:Protease Inhibitors; D020782:Matrix Metalloproteinases