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| EXAFS EVIDENCE FOR A CYSTEINE SWITCH IN THE ACTIVATION OF PROSTROMELYSIN |
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| Author(s): HOLZ RC, SALOWE SP, SMITH CK, CUCA GC, QUE L |
| Source: JOURNAL OF THE AMERICAN CHEMICAL SOCIETY Volume: 114 Issue: 24 Pages: 9611-9614 Published: NOV 18 1992 |
| Times Cited: 26 References: 30 |
| Abstract: Zn K-edge EXAFS data of the matrix metalloproteinase (MMP) stromelysin-I were obtained in both its latent proenzyme and mature active forms. The Fourier-filtered (back-transform 0.7-2.3 angstrom) (chi)k3 spectrum of mature stromelysin was satisfactorily simulated with 4 N/O scatterers per Zn at 2.01 angstrom, 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 angstrom. 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. |
| Document Type: Article |
| Language: English |
Addresses:
1. UNIV MINNESOTA, DEPT CHEM, MINNEAPOLIS, MN 55455 USA
2. MERCK SHARP & DOHME LTD, DEPT BIOPHYS CHEM, RAHWAY, NJ 07065 USA |
| Publisher: AMER CHEMICAL SOC, 1155 16TH ST, NW, WASHINGTON, DC 20036 |
| Subject Category: Chemistry, Multidisciplinary |
| IDS Number: JZ236 |
| ISSN: 0002-7863 |
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