scholarly journals Anomalous pH-dependence of the activity of human matrilysin (matrix metalloproteinase-7) as revealed by nitration and amination of its tyrosine residues

2005 ◽  
Vol 386 (2) ◽  
pp. 263-270 ◽  
Author(s):  
Yuko MUTA ◽  
Hiroshi ONEDA ◽  
Kuniyo INOUYE
Keyword(s):  
Matrix Metalloproteinase ◽  
Strong Influence ◽  
Negative Charge ◽  
Ph Dependence ◽  
Michaelis Constant ◽  
Pka Values ◽  
Tyrosine Residues ◽  
Alkaline Side ◽  
Matrix Metalloproteinase 7

Matrilysin activity exhibits a broad bell-shaped pH-dependence profile, with pKa values of 4.0 and 9.8. A maximum of five out of eight tyrosine residues in matrilysin were nitrated with tetranitromethane. On nitration of between one and five tyrosines, pKa at the alkaline side (pKe2) was shifted from 9.8 to 10.3–10.6, while that at the acidic side (pKe1) was not altered. The pKe2 that was shifted by nitration to 10.3–10.6 was restored to 9.4–9.7 by subsequent amination, suggesting that the shift in pKe2 is induced by a negative charge introduced on the most reactive tyrosine, Tyr-150. The Michaelis constant (Km) observed at pH 10 was decreased by nitration as a result of the increase in pKe2, suggesting that the residue with pKe2 may play a role in the recognition of substrate. When four or five tyrosines were nitrated, the activity at pH <7 decreased significantly, while that at pH 7–10 was unchanged, and thus the pH-dependence was not bell-shaped, but anomalous, with a third pKa (pKe3) of 6.2–6.4 in addition to pKe1 and pKe2. This suggests the possibility that a newly introduced nitrotyrosine residue has a strong influence on the activity as an ionizable group.

scholarly journals Divergent functions for airway epithelial matrix metalloproteinase 7 and retinoic acid in experimental asthma

2009 ◽  
Vol 10 (5) ◽  
pp. 496-503 ◽  
Author(s):  
Sangeeta Goswami ◽  
Pornpimon Angkasekwinai ◽  
Ming Shan ◽  
Kendra J Greenlee ◽  
Wade T Barranco ◽  
...  
Keyword(s):  
Retinoic Acid ◽  
Matrix Metalloproteinase ◽  
Airway Epithelial ◽  
Matrix Metalloproteinase 7

scholarly journals Current Concepts of Biliary Atresia and Matrix Metalloproteinase-7: A Review of Literature

2020 ◽  
Vol 7 ◽  
Author(s):  
Mark Nomden ◽  
Leonie Beljaars ◽  
Henkjan J. Verkade ◽  
Jan B. F. Hulscher ◽  
Peter Olinga
Keyword(s):  
Immune Response ◽  
Liver Fibrosis ◽  
Pulmonary Fibrosis ◽  
Matrix Metalloproteinase ◽  
Biliary Atresia ◽  
Adaptive Immune Response ◽  
Cell Contact ◽  
T Helper 1 ◽  
Matrix Metalloproteinase 7

Biliary atresia (BA) is a rare cholangiopathy of infancy in which the bile ducts obliterate, leading to profound cholestasis and liver fibrosis. BA is hypothesized to be caused by a viral insult that leads to over-activation of the immune system. Patients with BA are surgically treated with a Kasai portoenterostomy (KPE), which aims to restore bile flow from the liver to the intestines. After KPE, progressive liver fibrosis is often observed in BA patients, even despite surgical success and clearance of their jaundice. The innate immune response is involved during the initial damage to the cholangiocytes and further differentiation of the adaptive immune response into a T-helper 1 cell (Th1) response. Multiple studies have shown that there is continuing elevation of involved cytokines that can lead to the progressive liver fibrosis. However, the mechanism by which the progressive injury occurs is not fully elucidated. Recently, matrix metalloproteinase-7 (MMP-7) has been investigated to be used as a biomarker to diagnose BA. MMPs are involved in extracellular matrix (ECM) turnover, but also have non-ECM related functions. The role of MMP-7 and other MMPs in liver fibrosis is just starting to be elucidated. Multiple studies have shown that serum MMP-7 measurements are able to accurately diagnose BA in a cohort of cholestatic patients while hepatic MMP-7 expression correlated with BA-related liver fibrosis. While the mechanism by which MMP-7 can be involved in the pathophysiology of BA is unclear, MMP-7 has been investigated in other fibrotic pathologies such as renal and idiopathic pulmonary fibrosis. MMP-7 is involved in Wnt/β-catenin signaling, reducing cell-to-cell contact by shedding of E-cadherin, amplifying inflammation and fibrosis via osteopontin (OPN) and TNF-α while it also appears to play a role in induction of angiogenesis This review aims to describe the current understandings of the pathophysiology of BA. Subsequently, we describe how MMP-7 is involved in other pathologies, such as renal and pulmonary fibrosis. Then, we propose how MMP-7 can potentially be involved in BA. By doing this, we aim to describe the putative role of MMP-7 as a prognostic biomarker in BA and to provide possible new therapeutic and research targets that can be investigated in the future.

scholarly journals A Rationalization of the Acidic pH Dependence for Stromelysin-1 (Matrix Metalloproteinase-3) Catalysis and Inhibition

2000 ◽  
Vol 275 (15) ◽  
pp. 11026-11033 ◽  
Author(s):  
Linda L. Johnson ◽  
Alexander G. Pavlovsky ◽  
Adam R. Johnson ◽  
Jeffrey A. Janowicz ◽  
Chiu-Fai Man ◽  
...  
Keyword(s):  
Matrix Metalloproteinase ◽  
Ph Dependence ◽  
Acidic Ph ◽  
Matrix Metalloproteinase 3
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