title: Looking at the proteases from a simple perspective.
abstract: Proteases have received enormous interest from the research and medical communities because of their significant roles in several human diseases. Some examples include the involvement of thrombin in thrombosis, HIV-1 protease in Acquired Immune Deficiency Syndrome, cruzain in Trypanosoma cruzi infection, and membrane-type 1 matrix metalloproteinase in tumor invasion and metastasis. Many efforts has been undertaken to design effective inhibitors featuring potent inhibitory activity, specificity, and metabolic stability to those proteases involved in such pathologies. Protease inhibitors usually target the active site, but some of them act by other inhibitory mechanisms. The understanding of the structure-function relationships of proteases and inhibitors has an impact on new inhibitor drugs designing. In this paper, the structures of four proteases (thrombin, HIV-protease, cruzain, and a matrix metalloproteinase) are briefly reviewed, and used as examples of the importance of proteases for the development of new treatment strategies, leading to a longer and healthier life.
authors.affiliation: LABioMol, Departamento de Biologia Celular e Molecular, Instituto de Biologia, Universidade Federal Fluminense, Rio de Janeiro, 24001-970, Brazil. hcastrorangel@yahoo.com.br
authors.forename: Helena C
authors.initials: HC
authors.lastname: Castro
authors.forename: Paula A
authors.initials: PA
authors.lastname: Abreu
authors.forename: Reinaldo B
authors.initials: RB
authors.lastname: Geraldo
authors.forename: Rita C A
authors.initials: RC
authors.lastname: Martins
authors.forename: Ruben
authors.initials: R
authors.lastname: dos Santos
authors.forename: Natália I V
authors.initials: NI
authors.lastname: Loureiro
authors.forename: Lúcio M
authors.initials: LM
authors.lastname: Cabral
authors.forename: Carlos R
authors.initials: CR
authors.lastname: Rodrigues
mesh_terms: D003546:Cysteine Endopeptidases / Q000737:chemistry / Q000378:metabolism; D016333:HIV Protease / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D020782:Matrix Metalloproteinases / Q000737:chemistry / Q000378:metabolism; D010447:Peptide Hydrolases / Q000737:chemistry / Q000378:metabolism*; D057057:Serine Proteases / Q000737:chemistry / Q000378:metabolism
chemical_list: D010447:Peptide Hydrolases; D057057:Serine Proteases; D003546:Cysteine Endopeptidases; D016333:HIV Protease; D020782:Matrix Metalloproteinases