Contact details
Georgios A. Spyroulias, PhD.
Department of Pharmacy
University of Patras
Panepistimioupoli-Rion,
GR-26504 Patras, GREECE
Tel: +30.2610.969950 (office)
+30.2610.969951 (terra silico)
+30.2610.969952 (terra vitro)
Fax: +30.2610.969950
Email: G.A.Spyroulias@upatras.gr
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Now is: 2019-06-16 19:25
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| Zinc Metalloproteases – Conformational Dynamics and substrate selectivity |
 Zinc (Zn) metal ion is the second most abundant transition metal ion in living organism following iron. Zn(II) exhibits remarkable stability in redox processes due to its d10 electronic configuration and is known to be indispensable to growth and development, to metabolic pathways as well as to transmission of the genetic message.The coordination properties of the zinc allows the metal to bind within a broad range of tetrahedral sites in proteins and its role has found to be among others structural and/or catalytic. Zinc proteins may comprise the 10% of the human proteome with Zinc-metalloproteases being among them. Zn-proteases are enzymes where zinc participates in the proteolysis of peptides or polypeptides. Angiotensin-I Converting Enzyme, Neutral Endopeptidase and Endothelin Converting Enzyme are all enzymes that catalyze the proteolytic cleavage of short peptides (Angiotensin-I, Bradykinin, Endothelin, etc.) that are implicated in blood pressure regulation {Sturrock ED et al. Nat Rev Drug Discov. 2, 891-902, (2003)}. Anthrax Lethal Factor is a highly specific metalloprotease that cleaves most isoforms of the family of mitogen-activated protein kinase kinases (MEKs/MKKs) close to their amino termini, resulting in the inhibition of one or more signaling pathways {Duesbery NS et al. Cancer Res. 68, 81–88, (2008)}. All the above Zn-proteases belong to the gluzincin sub-family. Computational tools and experimental techniques are applied in order to draw atomic-level structural insights from enzyme-peptide/substrate complexes towards the understanding of enzyme selectivity and function. |
