Bioinformatic comparison of structures and homology-models of matrix metalloproteinases.
The entire family of human matrix metalloproteinases (MMPs) was investigated using phylogenetic trees and homology modeling. The phylogenetic analysis indicates that individual domains of each MMP have evolved in a correlated manner. Despite their high sequence similarity, the phylogenetic tree of the catalytic domains already allows functional (e.g., linked to regulation and substrate recognition) homologies between different MMPs to be identified. The same pattern of functional homologies is confirmed by the phylogenetic analysis of the mature proteins. Structural models were built for the catalytic domains of the entire MMP family, for twelve hemopexin domains and for twelve mature proteins. The surface properties around the active site cleft of the modeled and experimental structures are quite conserved, whereas the hemopexin domains are more differentiated, possibly indicating a role in determining substrate specificity. The analysis of mature MMPs showed that the area of the interface between the catalytic and hemopexin domains is essentially conserved, with both hydrophobic and hydrophilic amino acids at the interface. The absence of specific conserved interdomain contacts suggests that the interface is tolerant to amino acid replacements, and that there may be a certain degree of plasticity with respect to the reciprocal orientation of the two domains.
Magnetic Resonance Center (CERM), University of Florence, Via L. Sacconi 6, 50019 Sesto Fiorentino, Italy.
Claudia
C
Andreini
Lucia
L
Banci
Ivano
I
Bertini
Claudio
C
Luchinat
Antonio
A
Rosato
D001665:Binding Sites; D020134:Catalytic Domain; D019295:Computational Biology / Q000379:methods*; D006801:Humans; D020782:Matrix Metalloproteinases / Q000737:chemistry* / Q000235:genetics; D008958:Models, Molecular; D010802:Phylogeny; D040681:Structural Homology, Protein
D020782:Matrix Metalloproteinases