title: Screening of matrix metalloproteinases available from the protein data bank: insights into biological functions, domain organization, and zinc binding groups.
abstract: A total of 142 matrix metalloproteinase (MMP) X-ray crystallographic structures were retrieved from the Protein Data Bank (PDB) and analyzed by an automated and efficient routine, developed in-house, with a series of bioinformatic tools. Highly informative heat maps and hierarchical clusterograms provided a reliable and comprehensive representation of the relationships existing among MMPs, enlarging and complementing the current knowledge in the field. Multiple sequence and structural alignments permitted better location and display of key MMP motifs and quantification of the residue consensus at each amino acid position in the most critical binding subsites of MMPs. The MMP active site consensus sequences, the C-alpha root-mean-square deviation (RMSd) analysis of diverse enzymatic subsites, and the examination of the chemical nature, binding topologies, and zinc binding groups (ZBGs) of ligands extracted from crystallographic complexes provided useful insights on the structural arrangements of the most potent MMP inhibitors.
authors.affiliation: Dipartimento Farmaco-Chimico, University of Bari, via Orabona 4, I-70125 Bari, Italy.
authors.forename: Orazio
authors.initials: O
authors.lastname: Nicolotti
authors.forename: Teresa Fabiola
authors.initials: TF
authors.lastname: Miscioscia
authors.forename: Francesco
authors.initials: F
authors.lastname: Leonetti
authors.forename: Giovanni
authors.initials: G
authors.lastname: Muncipinto
authors.forename: Angelo
authors.initials: A
authors.lastname: Carotti
mesh_terms: D016000:Cluster Analysis; D018360:Crystallography, X-Ray; D030562:Databases, Protein; D004353:Drug Evaluation, Preclinical; D006358:Hot Temperature; D008024:Ligands; D020782:Matrix Metalloproteinases / Q000737:chemistry* / Q000378:metabolism*; D008958:Models, Molecular; D008968:Molecular Conformation; D008969:Molecular Sequence Data; D011485:Protein Binding; D015032:Zinc / Q000737:chemistry* / Q000378:metabolism*
chemical_list: D008024:Ligands; D020782:Matrix Metalloproteinases; D015032:Zinc