Catalytic- and ecto-domains of membrane type 1-matrix metalloproteinase have similar inhibition profiles but distinct endopeptidase activities

Hurst DR, Schwartz MA, Ghaffari MA, Jin YH, Tschesche H, Fields GB, Sang QXA (2004)
BIOCHEMICAL JOURNAL 377: 775-779.

Journal Article | Published | English

No fulltext has been uploaded

Author
; ; ; ; ; ;
Abstract
Membrane type 1-matrix metalloproteinase (MT1-MMP/MMP-14) is a major collagenolytic enzyme that plays a vital role in development and morphogenesis. To elucidate further the structure-function relationship between the human MT1-MMP active site and the influence of the haemopexin domain on catalysis, substrate specificity and inhibition kinetics of the cdMT1-MMP (catalytic domain of MT1-MMP) and the ecto domain DeltaTM-MT1-MMP (transmembrane-domain-deleted MT1-MMP) were compared. For substrate 1 [Mca-Pro-Leu-Gly-Leu-Dpa-Ala-Arg-NH2, where Mca stands for (7-methoxycoumarin-4-yl)acetyl- and Dpa for N-3-(2,4-dinitrophenyl)-L-2,3-diaminopropionyl], the activation energy E-a was determined to be 11.2 and 12.2 kcal/mol (1 cal = 4.184 J) for cdMT1-MMP and DeltaTM-MT1-MMP respectively, which is consistent with k(cat)/K-M values of 7.37 and 1.46 x 10(4) M-1. s(-1). The k(cat)/K-M values for a series of similar single-stranded peptide substrates were determined and found to correlate with a slope of 0.17 for the two enzyme forms. A triple-helical peptide substrate was predicted to have a k(cat)/K-M of 0.87 x 10(4) M-1 . s(-1) for DeltaTM-MT1-MMP based on the value for cdMT1-MMP of 5.12 x 10(4) M-1. s(-1); however, the actual value was determined to be 2.5-fold higher, i.e. 2.18 x 10(4) M-1. s(-1). These results suggest that cdMT1-MMP is catalytically more efficient towards small peptide substrates than ATM-MT1-MMP and the haernopexin domain of MT1-MMP facilitates the hydrolysis of triple-helical substrates. Diastereomeric inhibitor pairs were utilized to probe further binding similarities at the active site. Ratios of K-i values for the inhibitor pairs were found to correlate between the enzyme forms with a slope of 1.03, suggesting that the haernopexin domain does not significantly modify the enzyme active-site structure.
Publishing Year
ISSN
PUB-ID

Cite this

Hurst DR, Schwartz MA, Ghaffari MA, et al. Catalytic- and ecto-domains of membrane type 1-matrix metalloproteinase have similar inhibition profiles but distinct endopeptidase activities. BIOCHEMICAL JOURNAL. 2004;377:775-779.
Hurst, D. R., Schwartz, M. A., Ghaffari, M. A., Jin, Y. H., Tschesche, H., Fields, G. B., & Sang, Q. X. A. (2004). Catalytic- and ecto-domains of membrane type 1-matrix metalloproteinase have similar inhibition profiles but distinct endopeptidase activities. BIOCHEMICAL JOURNAL, 377, 775-779.
Hurst, D. R., Schwartz, M. A., Ghaffari, M. A., Jin, Y. H., Tschesche, H., Fields, G. B., and Sang, Q. X. A. (2004). Catalytic- and ecto-domains of membrane type 1-matrix metalloproteinase have similar inhibition profiles but distinct endopeptidase activities. BIOCHEMICAL JOURNAL 377, 775-779.
Hurst, D.R., et al., 2004. Catalytic- and ecto-domains of membrane type 1-matrix metalloproteinase have similar inhibition profiles but distinct endopeptidase activities. BIOCHEMICAL JOURNAL, 377, p 775-779.
D.R. Hurst, et al., “Catalytic- and ecto-domains of membrane type 1-matrix metalloproteinase have similar inhibition profiles but distinct endopeptidase activities”, BIOCHEMICAL JOURNAL, vol. 377, 2004, pp. 775-779.
Hurst, D.R., Schwartz, M.A., Ghaffari, M.A., Jin, Y.H., Tschesche, H., Fields, G.B., Sang, Q.X.A.: Catalytic- and ecto-domains of membrane type 1-matrix metalloproteinase have similar inhibition profiles but distinct endopeptidase activities. BIOCHEMICAL JOURNAL. 377, 775-779 (2004).
Hurst, DR, Schwartz, MA, Ghaffari, MA, Jin, YH, Tschesche, Harald, Fields, GB, and Sang, QXA. “Catalytic- and ecto-domains of membrane type 1-matrix metalloproteinase have similar inhibition profiles but distinct endopeptidase activities”. BIOCHEMICAL JOURNAL 377 (2004): 775-779.
This data publication is cited in the following publications:
This publication cites the following data publications:

16 Citations in Europe PMC

Data provided by Europe PubMed Central.

Collagenolytic Matrix Metalloproteinase Activities toward Peptomeric Triple-Helical Substrates.
Stawikowski MJ, Stawikowska R, Fields GB., Biochemistry 54(19), 2015
PMID: 25897652
Development of a Forster resonance energy transfer assay for monitoring bacterial collagenase triple-helical peptidase activity.
Tokmina-Roszyk M, Tokmina-Roszyk D, Bhowmick M, Fields GB., Anal. Biochem. 453(), 2014
PMID: 24608089
Matrix metalloproteinase inhibitors based on the 3-mercaptopyrrolidine core.
Jin Y, Roycik MD, Bosco DB, Cao Q, Constantino MH, Schwartz MA, Sang QX., J. Med. Chem. 56(11), 2013
PMID: 23631440
Structural basis for matrix metalloproteinase 1-catalyzed collagenolysis.
Bertini I, Fragai M, Luchinat C, Melikian M, Toccafondi M, Lauer JL, Fields GB., J. Am. Chem. Soc. 134(4), 2012
PMID: 22239621
The interface between catalytic and hemopexin domains in matrix metalloproteinase-1 conceals a collagen binding exosite.
Arnold LH, Butt LE, Prior SH, Read CM, Fields GB, Pickford AR., J. Biol. Chem. 286(52), 2011
PMID: 22030392
Regulation of matrix metalloproteinase activity in health and disease.
Hadler-Olsen E, Fadnes B, Sylte I, Uhlin-Hansen L, Winberg JO., FEBS J. 278(1), 2011
PMID: 21087458
Identification of specific hemopexin-like domain residues that facilitate matrix metalloproteinase collagenolytic activity.
Lauer-Fields JL, Chalmers MJ, Busby SA, Minond D, Griffin PR, Fields GB., J. Biol. Chem. 284(36), 2009
PMID: 19574232
Selective modulation of matrix metalloproteinase 9 (MMP-9) functions via exosite inhibition.
Lauer-Fields JL, Whitehead JK, Li S, Hammer RP, Brew K, Fields GB., J. Biol. Chem. 283(29), 2008
PMID: 18499673
Stir-baked Fructus gardeniae (L.) extracts inhibit matrix metalloproteinases and alter cell morphology.
Yang JG, Shen YH, Hong Y, Jin FH, Zhao SH, Wang MC, Shi XJ, Fang XX., J Ethnopharmacol 117(2), 2008
PMID: 18342464
Triple-helical transition state analogues: a new class of selective matrix metalloproteinase inhibitors.
Lauer-Fields J, Brew K, Whitehead JK, Li S, Hammer RP, Fields GB., J. Am. Chem. Soc. 129(34), 2007
PMID: 17672455
Differentiation of secreted and membrane-type matrix metalloproteinase activities based on substitutions and interruptions of triple-helical sequences.
Minond D, Lauer-Fields JL, Cudic M, Overall CM, Pei D, Brew K, Moss ML, Fields GB., Biochemistry 46(12), 2007
PMID: 17338550
Development of a solid-phase assay for analysis of matrix metalloproteinase activity.
Lauer-Fields JL, Nagase H, Fields GB., J Biomol Tech 15(4), 2004
PMID: 15585827

Export

0 Marked Publications

Open Data PUB

Web of Science

View record in Web of Science®

Sources

PMID: 14533979
PubMed | Europe PMC

Search this title in

Google Scholar