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Molecular dynamics simulation of Leishmania major surface metalloprotease GP63 (leishmanolysin)
- Source :
- Proteins: Structure, Function, and Bioinformatics. 64:385-390
- Publication Year :
- 2006
- Publisher :
- Wiley, 2006.
-
Abstract
- 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.
- Subjects :
- Models, Molecular
Protein Conformation
Stereochemistry
Molecular Conformation
Biochemistry
Protein Structure, Secondary
Enzyme activator
Molecular dynamics
Protein structure
Structural Biology
parasitic diseases
Animals
Humans
Computer Simulation
Leishmania major
Binding site
Molecular Biology
chemistry.chemical_classification
Binding Sites
biology
Solvation
Metalloendopeptidases
Active site
Hydrogen-Ion Concentration
biology.organism_classification
Protein Structure, Tertiary
Matrix Metalloproteinase 8
Enzyme
chemistry
Metalloproteases
Biophysics
biology.protein
Subjects
Details
- ISSN :
- 08873585
- Volume :
- 64
- Database :
- OpenAIRE
- Journal :
- Proteins: Structure, Function, and Bioinformatics
- Accession number :
- edsair.doi.dedup.....8557ab5eeb3594842d6d37136285b031