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Science 4 June 1999:
Vol. 284. no. 5420, pp. 1667 - 1670
DOI: 10.1126/science.284.5420.1667
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Reports

Structure of Human Pro-Matrix Metalloproteinase-2: Activation Mechanism Revealed

Ekaterina Morgunova, 12 Ari Tuuttila, 1 Ulrich Bergmann, 1 Mikhail Isupov, 3 Ylva Lindqvist, 2 Gunter Schneider, 2* Karl Tryggvason 1*

Matrix metalloproteinases (MMPs) catalyze extracellular matrix degradation. Control of their activity is a promising target for therapy of diseases characterized by abnormal connective tissue turnover. MMPs are expressed as latent proenzymes that are activated by proteolytic cleavage that triggers a conformational change in the propeptide (cysteine switch). The structure of proMMP-2 reveals how the propeptide shields the catalytic cleft and that the cysteine switch may operate through cleavage of loops essential for propeptide stability.

1 Division of Matrix Biology, Department of Medical Biochemistry and Biophysics and
2 Division of Molecular Structural Biology, Department of Medical Biochemistry and Biophysics, Karolinska Institute, Stockholm, Sweden.
3 Schools of Chemistry and Biological Sciences, University of Exeter, UK.
*   To whom correspondence should be addressed. E-mail: gunter{at}alfa.mbb.ki.se (G.S.); karl.tryggvason{at}mbb.ki.se (K.T.).

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L. Chung, K.-i. Shimokawa, D. Dinakarpandian, F. Grams, G. B. Fields, and H. Nagase (2000)
J. Biol. Chem. 275, 29610-29617
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Structural Characterization of the Catalytic Active Site in the Latent and Active Natural Gelatinase B from Human Neutrophils.
O. Kleifeld, P. E. Van den Steen, A. Frenkel, F. Cheng, H. L. Jiang, G. Opdenakker, and I. Sagi (2000)
J. Biol. Chem. 275, 34335-34343
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E. A. Hahn-Dantona, R. T. Aimes, and J. P. Quigley (2000)
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H. Brandstetter, F. Grams, D. Glitz, A. Lang, R. Huber, W. Bode, H.-W. Krell, and R. A. Engh (2001)
J. Biol. Chem. 276, 17405-17412
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X-ray Absorption Studies of Human Matrix Metalloproteinase-2 (MMP-2) Bound to a Highly Selective Mechanism-based Inhibitor. COMPARISON WITH THE LATENT AND ACTIVE FORMS OF THE ENZYME.
O. Kleifeld, L. P. Kotra, D. C. Gervasi, S. Brown, M. M. Bernardo, R. Fridman, S. Mobashery, and I. Sagi (2001)
J. Biol. Chem. 276, 17125-17131
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Involvement of Fibronectin Type II Repeats in the Efficient Inhibition of Gelatinases A and B by Long-chain Unsaturated Fatty Acids.
A. Berton, V. Rigot, E. Huet, M. Decarme, Y. Eeckhout, L. Patthy, G. Godeau, W. Hornebeck, G. Bellon, and H. Emonard (2001)
J. Biol. Chem. 276, 20458-20465
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Substrate Hydrolysis by Matrix Metalloproteinase-9*.
S. J. Kridel, E. Chen, L. P. Kotra, E. W. Howard, S. Mobashery, and J. W. Smith (2001)
J. Biol. Chem. 276, 20572-20578
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Gelatin-binding Region of Human Matrix Metalloproteinase-2. SOLUTION STRUCTURE, DYNAMICS, AND FUNCTION OF THE COL-23 TWO-DOMAIN CONSTRUCT.
K. Briknarova, M. Gehrmann, L. Banyai, H. Tordai, L. Patthy, and M. Llinas (2001)
J. Biol. Chem. 276, 27613-27621
   Abstract »    Full Text »    PDF »


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