From the X-ray compact structure to the elongated form of the full-length MMP-2 enzyme in solution: a molecular dynamics study.
Current understanding on the collagenolytic activity performed by the MMPs assumes some degree of relative motion between the catalytic and the hemopexin-like domains of the enzyme. However, all the crystal structures available for the full-length enzymes display a compact arrangement of the protein domains. Herein, we employ Molecular Dynamics simulations to investigate the structure of the full-length MMP-2 enzyme in aqueous solution. This simulation, together with previous experimental results that have been obtained very recently for the MMP-9 and MMP-12 enzymes, gives strong support to the hypothesis that the interdomain dynamics of the MMP enzymes in solution can result in a manifold of conformations including some structures with a large interdomain separation. The simulation of MMP-2 provides also a detailed molecular picture of the structures involved in the transition from the compact X-ray arrangement to the extended form in solution. Such information could be helpful in future studies of the regulation and/or the collagenolytic activity of these important enzymes.
Díaz
Natalia
N
Universidad de Oviedo, Dpto. Química Física y Analítica, C/Julián Clavería, 8, 33006 (Oviedo) Asturias, Spain. diazfnatalia@uniovi.es
Suárez
Dimas
D
Valdés
Haydee
H
D003198:Computer Simulation; D018360:Crystallography, X-Ray; D020778:Matrix Metalloproteinase 2 / Q000737:chemistry*; D008956:Models, Chemical; D008958:Models, Molecular; D017434:Protein Structure, Tertiary; D012996:Solutions / Q000737:chemistry
D012996:Solutions; D020778:Matrix Metalloproteinase 2