High-Throughput Multiplexed Peptide-Centric Profiling Illustrates Both Substrate Cleavage Redundancy and Specificity in the MMP Family.

@article{Kukreja2015HighThroughputMP,
  title={High-Throughput Multiplexed Peptide-Centric Profiling Illustrates Both Substrate Cleavage Redundancy and Specificity in the MMP Family.},
  author={Muskan Kukreja and S. Shiryaev and P. Cieplak and Norihito Muranaka and D. Routenberg and A. Chernov and Sonu Kumar and A. Remacle and Jeffrey W. Smith and I. Kozlov and A. Strongin},
  journal={Chemistry \& biology},
  year={2015},
  volume={22 8},
  pages={
          1122-33
        }
}
Matrix metalloproteinases (MMPs) play incompletely understood roles in health and disease. Knowing the MMP cleavage preferences is essential for a better understanding of the MMP functions and design of selective inhibitors. To elucidate the cleavage preferences of MMPs, we employed a high-throughput multiplexed peptide-centric profiling technology involving the cleavage of 18,583 peptides by 18 proteinases from the main sub-groups of the MMP family. Our results enabled comparison of the MMP… Expand

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References

SHOWING 1-10 OF 62 REFERENCES
Proteomics Discovery of Metalloproteinase Substrates in the Cellular Context by iTRAQ™ Labeling Reveals a Diverse MMP-2 Substrate Degradome*S
TLDR
“Peptide mapping,” the location of multiple peptides identified within a particular protein by iTRAQ in combination with their relative abundance ratios, enabled the domain shed and general location of the cleavage site to be identified in the native cellular substrate. Expand
High-Resolution Analysis and Functional Mapping of Cleavage Sites and Substrate Proteins of Furin in the Human Proteome
TLDR
An approach for proteinase target identification that combines an in silico discovery pipeline with highly multiplexed proteinase activity assays is devised and suggests an important role of furin in development, including axonal guidance, cardiogenesis, and maintenance of stem cell pluripotency. Expand
Determination of protease cleavage site motifs using mixture-based oriented peptide libraries
TLDR
The results indicate that a small set of libraries can be used to quickly profile an expanding protease family, providing information applicable to the design of inhibitors and to the identification of protein substrates. Expand
A Unique Substrate Recognition Profile for Matrix Metalloproteinase-2*
TLDR
It is indicated that M MP-2 and MMP-9 exhibit different substrate recognition profiles and point to the P2 subsite as a primary determinant in substrate distinction. Expand
Proteomic approaches to uncover MMP function.
TLDR
An overview of current proteomic technologies in protease research and their application to the functional characterization of MMPs is provided. Expand
High throughput substrate phage display for protease profiling.
TLDR
This work has characterized protease specificities of several matrix metalloproteinases using substrate phage display using a semiautomated platform that includes several high-throughput steps and allows precise comparisons among related proteases to define their functional distinctions. Expand
Proteomic discovery of protease substrates.
TLDR
In vivo SILAC pulse-chase experiments have enabled the study of individual protein turnover and global proteome dynamics in cells and whole organisms, and there is now in place an array of complementary technologies to dissect the 'protease web' and its distortion in pathology. Expand
Metadegradomics: toward in vivo quantitative degradomics of proteolytic post-translational modifications of the cancer proteome.
TLDR
Recent degradomics technologies that allow for the broadly applicable identification and quantification of proteases (the protease degradome) and their activity state, substrates, and interactors are reviewed. Expand
Basis for substrate recognition and distinction by matrix metalloproteinases
TLDR
Estimating structure–function relationships among three phylogenetic branches of the matrix metalloproteinase (MMP) family by comparing their cleavage efficiencies toward an extended set of phage peptide substrates that were selected from ∼64 million peptide sequences provides a distance measure of functional similarity among the MMPs. Expand
CleavPredict: A Platform for Reasoning about Matrix Metalloproteinases Proteolytic Events
TLDR
The server provides information about subcellular location, co-localization, and co-expression of proteinase and potential substrates, along with experimentally determined positions of single nucleotide polymorphism (SNP), and posttranslational modification (PTM) sites in substrates. Expand
...
1
2
3
4
5
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