Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.24.3 (collagenase)
 18,340 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Matrix metalloproteinases (MMPs) are enzymes with critical roles in biology and pathology. Glycosylation, nitrosylation and proteolysis are known posttranslational modifications (PTMs) regulating intrinsically the activities of MMPs. We discovered MMP citrullination by peptidyl arginine deiminases (PADs) as a new PTM. Upon hypercitrullination, MMP-9 acquired a higher affinity for gelatin than control MMP-9. Furthermore, hypercitrullinated proMMP-9 was more efficiently activated by MMP-3 compared to control MMP-9. JNJ0966, a specific therapeutic inhibitor of MMP-9 activation, inhibited the activation of hypercitrullinated proMMP-9 by MMP-3 significantly less in comparison with control proMMP-9. The presence of citrullinated/homocitrullinated MMP-9 was detected in vivo in neutrophil-rich sputum samples of cystic fibrosis patients. In addition to citrullination of MMP-9, we report efficient citrullination of MMP-1 and lower citrullination levels of MMP-3 and MMP-13 by PAD2 in vitro. In conclusion, citrullination of MMPs is a new PTM worthy of additional biochemical and biological studies.
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PMID:Citrullination as a novel posttranslational modification of matrix metalloproteinases. 3315 27