EXAFS Evidence for a "Cysteine Switch" in the Activation of Prostromelysin

Document Type

Article

Publication Date

1992

Source Publication

Journal of the American Chemical Society

Source ISSN

0002-7863

Abstract

Zn K-edge EXAFS data of the matrix metalloproteinase (MMP) stromelysin-1 were obtained in both its latent proenzyme and mature active forms. The Fourier-filtered (back-transform 0.7-2.3 Å) xk3 spectrum of mature stromelysin was satisfactorily simulated with 4 N / O scatterers per Zn at 2.01 Å, while similar fits for prostromelysin were judged unacceptable because of unreasonable Debye-Waller factors or significantly larger residuals of the fits. For prostromelysin, excellent fits were obtained with the introduction of a sulfur scatterer at 2.25 Å. These data provide the first direct evidence for the coordination of zinc by the sole cysteine in the N-terminal domain of prostromelysin and confirm that the cysteine is lost upon activation. These results provide support for a "cysteine switch" structural model for MMP proenzymes that suggests the interaction of the conserved propeptide cysteine with zinc is present in the latent form. Examination of the Zn-S bond length and outer shell carbon contributions suggests that the 2 g-atoms of zinc recently shown to be present in stromelysin (Salowe, S.P., et al. Biochemistry 1992, 31, 4535-4540) reside in independent zinc sites.

Comments

Journal of the American Chemical Society, Vol. 114, No. 24 (1992): 9611-9614. DOI.

Richard Holz was affiliated with the University of Minnesota - Twin Cities at the time of publication.

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