Substrate specificity of human fibroblast stromelysin. Hydrolysis of substance P and its analogues.

Biochemistry
J TeahanR Stein

Abstract

To probe the substrate specificity of the human metalloproteinase stromelysin (SLN), we determined values of kc/Km for the SLN-catalyzed hydrolysis of substance P (Arg-Pro-Lys-Pro-Gln-Gln-Phe-Phe-Gly-Leu-MetNH2; SP; kc/Km = 1790 +/- 140 M-1 s-1), 15 analogues of SP, and 17 other peptides. We found a remarkably narrow substrate specificity for SLN: while SP and its analogues could serve as substrates for SLN (hydrolysis occurred exclusively at the Gln6-Phe7 bond), peptides that were not direct analogues could not (kc/Km less than 3 M-1 s-1). From the study of the SLN-catalyzed hydrolysis of SP and its analogues, the following findings emerged: (1) Decreasing the length of SP results in decreases in kc/Km. (2) Conservative amino acid replacements near the scissle bond of SP decrease kc/Km. (3) The SP analogue in which Gly9 is replaced with sarcosine (N-methylglycine) is not hydrolyzed by SLN (kc/Km less than 3 M-1 s-1). (4) Several SP analogues that are not hydrolyzed by SLN are inhibitors of the enzyme. The complexes formed from interaction of SLN with these peptides have dissociation constants that are similar to the Km value for the complex of SLN and SP. Combined, these results suggest that SLN uses the energy that is availab...Continue Reading

References

Jan 2, 1986·European Journal of Biochemistry·G ChassaingS Lavielle
Sep 1, 1988·Analytical Biochemistry·T Higa, D M Desiderio
Jul 1, 1988·Collagen and Related Research·G MurphyC E Brinckerhoff
Oct 1, 1988·The Journal of Histochemistry and Cytochemistry : Official Journal of the Histochemistry Society·M W LarkT N Wight
Jan 1, 1988·Journal of Orthopaedic Research : Official Publication of the Orthopaedic Research Society·C B CaputoG DiPasquale
Nov 19, 1974·Proceedings of the Royal Society of London. Series B, Containing Papers of a Biological Character·A R Fersht
Apr 20, 1967·Biochemical and Biophysical Research Communications·I Schechter, A Berger
Mar 1, 1984·Arthritis and Rheumatism·T E CawstonB L Hazleman

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Citations

Aug 23, 2008·Archives of Dermatological Research·Ilkka T HarvimaAnita Naukkarinen
Jul 1, 1993·Bioorganic & Medicinal Chemistry·M Izquierdo-Martin, R L Stein
Feb 13, 2001·European Journal of Biochemistry·B ArzaH R Lijnen
Sep 6, 1994·Annals of the New York Academy of Sciences·D M BickettG M McGeehan
Apr 1, 1991·Kidney International·K D GardnerR M Locksley
May 15, 1991·Analytical Biochemistry·S Netzel-ArnettH E Van Wart
Nov 10, 1992·Biochemistry·R K HarrisonR L Stein
Dec 26, 2001·Chemical Reviews·M WhittakerA J Gearing
Jun 2, 2007·Journal of the American Chemical Society·Mahesh UttamchandaniShao Q Yao

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