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Journal of Amino Acids
Volume 2011 (2011), Article ID 574816, 7 pages
Review Article

Metal Preferences of Zinc-Binding Motif on Metalloproteases

1Department of Hard Tissue Research, Graduate School of Oral Medicine, Matsumoto Dental University, Shiojiri, Nagano 399-0781, Japan
2Faculty of Pharmacy and Pharmaceutical Science, Fukuyama University, Gakuen-cho, Fukuyama 729-0292, Japan

Received 4 October 2010; Revised 25 January 2011; Accepted 7 March 2011

Academic Editor: Shandar Ahmad

Copyright © 2011 Kayoko M. Fukasawa et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


Almost all naturally occurring metalloproteases are monozinc enzymes. The zinc in any number of zinc metalloproteases has been substituted by some other divalent cation. Almost all Co(II)- or Mn(II)-substituted enzymes maintain the catalytic activity of their zinc counterparts. However, in the case of Cu(II) substitution of zinc proteases, a great number of enzymes are not active, for example, thermolysin, carboxypeptidase A, endopeptidase from Lactococcus lactis, or aminopeptidase B, while some do have catalytic activity, for example, astacin (37%) and DPP III (100%). Based on structural studies of various metal-substituted enzymes, for example, thermolysin, astacin, aminopeptidase B, dipeptidyl peptidase (DPP) III, and del-DPP III, the metal coordination geometries of both active and inactive Cu(II)-substituted enzymes are shown to be the same as those of the wild-type Zn(II) enzymes. Therefore, the enzyme activity of a copper-ion-substituted zinc metalloprotease may depend on the flexibility of catalytic domain.