ArticleProceedings of the National Academy of Sciences of the United States of America2014
Basis for substrate recognition and distinction by matrix metalloproteinases.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 61 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
61 citing papers in PubMed.
- Computational design of metalloproteases.Nature · 2026Article
- Chemical basis of fluorogenic substrate probe design: revisiting the past to discover the new in biochemistry.RSC chemical biology · 2026Review
- ProNotch converts extracellular protease activity into programmable transcriptional outputs.bioRxiv : the preprint server for biology · 2026Article
- Precision nanomedicine for lung metastatic osteosarcoma: challenges, therapeutic strategies, and perspectives.Materials today. Bio · 2026Review
- Urinary detection of therapy-induced senescence and fibrosis using an injectable albumin-based nanoprobe.Nature aging · 2026Article
- Microbial dl-Peptidases Enable Predator Defense and Facilitate Structure Elucidation of Complex Natural Products.Journal of the American Chemical Society · 2026Article
- Article
- Deep learning guided design of protease substrates.Nature communications · 2026Article
- Using High-Throughput Screening to Identify Crosslinking Peptides That Control Cell-Mediated Matrix Degradation.Advanced healthcare materials · 2025Article
- Computational design of metalloproteases.bioRxiv : the preprint server for biology · 2025Article
- Chemical probes for enzyme imaging: challenges in design, synthesis and biomedical applications.Chemical science · 2025Review
- DIVERGE v4: A Platform for Large-Scale Analysis of Functional Divergence Across Multi-Gene Families.Molecular biology and evolution · 2025Article
- Protease engineering: Approaches, tools, and emerging trends.Biotechnology advances · 2025Review
- PERRC: Protease Engineering with Reactant Residence Time Control.ACS synthetic biology · 2025Article
- Article
- Comprehensive investigation of matrix metalloproteinases in skin cutaneous melanoma: diagnostic, prognostic, and therapeutic insights.Scientific reports · 2025Article
- Novel Insights into the Catalytic Mechanism of Collagenolysis by Zn(II)-Dependent Matrix Metalloproteinase-1.Biochemistry · 2024Article
- Dabsylated Bradykinin Is Cleaved by Snake Venom Proteases fromBiomedicines · 2024Article
- In situ formed depot of elastin-like polypeptide-hirudin fusion protein for long-acting antithrombotic therapy.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- A Systematic Investigation of Proteoforms with N-Terminal Glycine and Their Dynamics Reveals Its Impacts on Protein Stability.Angewandte Chemie (International ed. in English) · 2024Article
1 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
13 authors.
Funding
Abstract
Genomic sequencing and structural genomics produced a vast amount of sequence and structural data, creating an opportunity for structure-function analysis in silico [Radivojac P, et al. (2013) Nat Methods 10(3):221-227]. Unfortunately, only a few large experimental datasets exist to serve as benchmarks for function-related predictions. Furthermore, currently there are no reliable means to predict the extent of functional similarity among proteins. Here, we quantify 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 (i.e., a large unbiased representation of substrate space). The observed second-order rate constants [k(obs)] across the substrate space provide a distance measure of functional similarity among the MMPs. These functional distances directly correlate with MMP phylogenetic distance. There is also a remarkable and near-perfect correlation between the MMP substrate preference and sequence identity of 50-57 discontinuous residues surrounding the catalytic groove. We conclude that these residues represent the specificity-determining positions (SDPs) that allowed for the expansion of MMP proteolytic function during evolution. A transmutation of only a few selected SDPs proximal to the bound substrate peptide, and contributing the most to selectivity among the MMPs, is sufficient to enact a global change in the substrate preference of one MMP to that of another, indicating the potential for the rational and focused redesign of cleavage specificity in MMPs.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.