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Molecular dynamics simulation of Leishmania major surface metalloprotease GP63 (leishmanolysin)
Author(s) -
Bianchini Gianluca,
Bocedi Alessio,
Ascenzi Paolo,
Gavuzzo Enrico,
Mazza Fernando,
Aschi Massimiliano
Publication year - 2006
Publication title -
proteins: structure, function, and bioinformatics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.699
H-Index - 191
eISSN - 1097-0134
pISSN - 0887-3585
DOI - 10.1002/prot.21009
Subject(s) - molecular dynamics , substrate (aquarium) , chemistry , biophysics , leishmania , metalloproteinase , virulence , relaxation (psychology) , solvation , dynamics (music) , enzyme , chemical physics , biology , solvent , biochemistry , physics , computational chemistry , gene , neuroscience , ecology , parasite hosting , world wide web , computer science , acoustics
One of the molecular factors contributing to Leishmania sp. virulence and pathogenesis is the major surface metalloprotease GP63, alternatively called leishmanolysin, MSP, and PSP (EC 3.4.24.36). Here, the molecular dynamics simulation of Leishmania major GP63 in water at pH 7 is reported. Upon solvation, GP63 undergoes a sharp structural relaxation with respect to the crystal structure. The fluctuation pattern occurs essentially in solvent‐exposed nonstructured regions. By contrast, the active site turns out to be rigid. Essential dynamics and dynamic‐domain analyses, both carried out on the equilibrated portion of GP63, show that the fingerprint fluctuations of GP63 are practically characterized by the motion of a large part of the N‐terminal domain. These results appear to be in line with substrate recognition and (pro)enzyme activation played by the N‐terminal domain of GP63. A systematic analysis among a series of 10 homologs of GP63 also shows that the residues involved in the interdomain bending result highly conserved. This finding also suggests possible relationship between the maintainance of proteolytic activity and the similarity of the dynamical properties of the related enzymes. Proteins 2006. © 2006 Wiley‐Liss, Inc.