Proteomics

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Active Site Specificity Profiling of the Matrix Metalloproteinase Family: Proteomic Identification of 4,300 Cleavage Sites by MMPs 1, 2, 3, 7, 8, 9, 12, 13, and 14.


ABSTRACT: Background: The active site of matrix metalloproteinases (MMPs) is highly conserved, complicating the rational design of specific substrates and inhibitors for individual family members. Results: Active site specificity profiles of 9 MMPs were determined using high throughput Proteomic Identification of protease Cleavage Sites (PICS). Conclusion: Subtle specificity divergences distinguish individual MMP family members. Significance: Understanding individual MMP cleavage site specificities will bolster the design of MMP specific activity assays and targeted inhibitory drugs.

INSTRUMENT(S): QSTAR XL, QSTAR Pulsar

ORGANISM(S): Homo Sapiens (human)

SUBMITTER: Ulrich ECKHARD  

LAB HEAD: Prof. Christopher Mark Overall

PROVIDER: PXD002265 | Pride | 2015-09-29

REPOSITORIES: Pride

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Publications

Active site specificity profiling of the matrix metalloproteinase family: Proteomic identification of 4300 cleavage sites by nine MMPs explored with structural and synthetic peptide cleavage analyses.

Eckhard Ulrich U   Huesgen Pitter F PF   Schilling Oliver O   Bellac Caroline L CL   Butler Georgina S GS   Cox Jennifer H JH   Dufour Antoine A   Goebeler Verena V   Kappelhoff Reinhild R   Keller Ulrich Auf dem UAD   Klein Theo T   Lange Philipp F PF   Marino Giada G   Morrison Charlotte J CJ   Prudova Anna A   Rodriguez David D   Starr Amanda E AE   Wang Yili Y   Overall Christopher M CM  

Matrix biology : journal of the International Society for Matrix Biology 20150925


Secreted and membrane tethered matrix metalloproteinases (MMPs) are key homeostatic proteases regulating the extracellular signaling and structural matrix environment of cells and tissues. For drug targeting of proteases, selectivity for individual molecules is highly desired and can be met by high yield active site specificity profiling. Using the high throughput Proteomic Identification of protease Cleavage Sites (PICS) method to simultaneously profile both the prime and non-prime sides of the  ...[more]

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