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Rodent α‐chymases Are Elastase‐like Proteases

Y. Kunori, Masahiro Koizumi, T. Masegi, H. Kasai, H. Kawabata, Y. Yamazaki, A. Fukamizu
Published 2002 · Biology

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Although the α-chymases of primates and dogs are known as chymotrypsin-like proteases, the enzymatic properties of rodent α-chymases (rat mast cell protease 5/rMCP-5 and mouse mast cell protease 5/mMCP-5) have not been fully understood. We report that recombinant rMCP-5 and mMCP-5 are elastase-like proteases, not chymotrypsin-like proteases. An enzyme assay using chromogenic peptidyl substrates showed that mast cell protease-5s (MCP-5s) have a clear preference for small aliphatic amino acids (e.g. alanine, isoleucine, valine) in the P1 site of substrates. We used site-directed mutagenesis and computer modeling approaches to define the determinant residue for the substrate specificity of mMCP-5, and found that the mutant possessing a Gly substitution of the Val at position 216 (V216G) lost elastase-like activity but acquired chymase activity, suggesting that the Val216 dominantly restricts the substrate specificity of mMCP-5. Structural models of mMCP-5 and the V216G mutant based on the crystal structures of serine proteases (rMCP-2, human cathepsin G, and human chymase) revealed the active site differences that can account for the marked differences in substrate specificity of the two enzymes between elastase and chymase. These findings suggest that rodent α-chymases have unique biological activity different from the chymases of other species.
This paper references
10.1038/227680A0
Cleavage of Structural Proteins during the Assembly of the Head of Bacteriophage T4
U. Laemmli (1970)
10.1073/PNAS.94.17.9017
Chymase cleavage of stem cell factor yields a bioactive, soluble product.
B. Longley (1997)
10.1016/0065-2571(86)90017-8
Biological functions of serine proteases in the granules of rat mast cells.
N. Katunuma (1986)
10.1152/ajpheart.1997.273.4.H1769
Angiotensin II formation from ACE and chymase in human and animal hearts: methods and species considerations.
E. Balcells (1997)
10.1042/BJ2940127
Biochemical and immunological characterization of multiple glycoforms of mouse mast cell protease 1: comparison with an isolated murine serosal mast cell protease (MMCP-4).
G. Newlands (1993)
10.1016/S0167-4838(00)00076-5
Angiotensin II generation by mast cell α- and β-chymases
G. Caughey (2000)
10.1161/01.CIR.99.8.1084
Tranilast suppresses vascular chymase expression and neointima formation in balloon-injured dog carotid artery.
N. Shiota (1999)
10.1016/0378-1119(89)90358-2
Site-directed mutagenesis by overlap extension using the polymerase chain reaction.
S. Ho (1989)
10.1098/RSTB.1970.0013
The three-dimensional structure of crystalline porcine pancreatic elastase.
D. Shotton (1970)
10.1165/AJRCMB.18.4.2536
Mast cell collagenase correlates with regression of pulmonary vascular remodeling in the rat.
C. A. Tozzi (1998)
10.1016/S0014-5793(02)02242-1
Evidence for diversity of substrate specificity among members of the chymase family of serine proteases
S. Solivan (2002)
10.1254/JJP.84.449
The functional ratio of chymase and angiotensin converting enzyme in angiotensin I-induced vascular contraction in monkeys, dogs and rats.
D. Jin (2000)
10.1111/j.1749-6632.1994.tb39789.x
Release and Inactivation of Interleukin‐4 by Mast Cells a
J. Lara (1994)
Human mucus proteinase inhibitor (human MPI). Human seminal inhibitor I (HUSI-I), antileukoprotease (ALP), secretory leukocyte protease inhibitor (SLPI).
H. Fritz (1988)
10.3181/00379727-203-43595
Interaction of Osteoblasts with Extracellular Matrix: Effect of Mast Cell Chymase
K. Banovac (1993)
10.1016/0014-5793(93)81348-4
Activation of two angiotensin‐generating systems in the balloon‐injured artery
N. Shiota (1993)
10.1038/sj.bjp.0702223
Human mast cell chymase induces the accumulation of neutrophils, eosinophils and other inflammatory cells in vivo
S. He (1998)
10.1021/BI00528A022
Mapping the active sites of bovine thrombin, factor IXa, factor Xa, factor XIa, factor XIIa, plasma kallikrein, and trypsin with amino acid and peptide thioesters: development of new sensitive substrates.
B. J. McRae (1981)
10.1016/0020-711x(93)90535-m
The Mast Cell in Health and Disease
M. Kaliner (1992)
10.1016/s0021-9258(18)54925-5
Molecular cloning of the mouse mast cell protease-5 gene. A novel secretory granule protease expressed early in the differentiation of serosal mast cells.
H. McNeil (1991)
10.1016/s0021-9258(18)54981-4
Multiple determinants for the high substrate specificity of an angiotensin II-forming chymase from the human heart.
A. Kinoshita (1991)
10.1038/sj.jhh.1000745
Effect of an angiotensin II receptor antagonist, candesartan cilexetil, on canine intima hyperplasia after balloon injury
M. Miyazaki (1999)
10.1021/BI00431A001
Human leukocyte and porcine pancreatic elastase: X-ray crystal structures, mechanism, substrate specificity, and mechanism-based inhibitors.
W. Bode (1989)
10.1084/JEM.174.4.821
Rapid and specific conversion of precursor interleukin 1 beta (IL-1 beta) to an active IL-1 species by human mast cell chymase
H. Mizutani (1991)
10.1002/jlb.67.4.585
Chymase is a potent chemoattractant for human monocytes and neutrophils
K. Tani (2000)
10.1016/0006-291X(90)90823-6
The mast cell as an effector of connective tissue degradation: a study of matrix susceptibility to human mast cells.
B. Gruber (1990)
10.1042/BJ3110675
Cloning of the cDNA encoding a novel rat mast-cell proteinase, rMCP-3, and its expression in comparison with other rat mast-cell proteinases.
H. Ide (1995)
10.1073/PNAS.84.2.364
Substrate specificity of the chymotrypsin-like protease in secretory granules isolated from rat mast cells.
H. Le Trong (1987)
10.1111/j.1440-1681.1997.tb01814.x
ANGIOTENSIN II‐GENERATING SYSTEM IN DOG AND MONKEY OCULAR TISSUES
N. Shiota (1997)
10.1074/JBC.270.9.4689
Human Mast Cell Chymase and Leukocyte Elastase Release Latent Transforming Growth Factor-β1 from the Extracellular Matrix of Cultured Human Epithelial and Endothelial Cells (*)
J. Taipale (1995)
Mast cell chymase. A potent secretagogue for airway gland serous cells.
C. Sommerhoff (1989)
10.1126/science.271.5248.502
Angiotensin II-Forming Activity in a Reconstructed Ancestral Chymase
U. Chandrasekharan (1996)
10.1146/ANNUREV.BI.46.070177.001555
Serine proteases: structure and mechanism of catalysis.
J. Kraut (1977)
Role of proteolysis and apoptosis in regression of pulmonary vascular remodeling.
D. J. Riley (2000)
10.1097/00004872-199715040-00014
Activation of angiotensin II‐forming chymase in the cardiomyopathic hamster heart
N. Shiota (1997)
10.1006/JMBI.1993.1626
Comparative protein modelling by satisfaction of spatial restraints.
A. S̆ali (1993)
10.1093/NAR/22.22.4673
CLUSTAL W: improving the sensitivity of progressive multiple sequence alignment through sequence weighting, position-specific gap penalties and weight matrix choice.
J. Thompson (1994)
10.1159/000236348
The effect of mast cell chymase on extracellular matrix: studies in autoimmune thyroiditis and in cultured thyroid cells.
K. Banovac (1992)
10.1021/BI00329A037
Mammalian chymotrypsin-like enzymes. Comparative reactivities of rat mast cell proteases, human and dog skin chymases, and human cathepsin G with peptide 4-nitroanilide substrates and with peptide chloromethyl ketone and sulfonyl fluoride inhibitors.
J. Powers (1985)
10.1006/JMBI.1999.2691
The 2.2 A crystal structure of human chymase in complex with succinyl-Ala-Ala-Pro-Phe-chloromethylketone: structural explanation for its dipeptidyl carboxypeptidase specificity.
P. J. Pereira (1999)
10.1084/JEM.185.1.13
Secretory Granule Proteases in Rat Mast Cells. Cloning of 10 Different Serine Proteases and a Carboxypeptidase A from Various Rat Mast Cell Populations
C. Lützelschwab (1997)
10.1016/s0021-9258(18)45712-2
Identification of a highly specific chymase as the major angiotensin II-forming enzyme in the human heart.
H. Urata (1990)
10.1073/PNAS.87.8.3230
Different mouse mast cell populations express various combinations of at least six distinct mast cell serine proteases.
D. Reynolds (1990)
10.1515/bchm.1998.379.7.885
Human Chymase, an Enzyme Forming Novel Bioactive 31-Amino Acid Length Endothelins
H. Kido (1998)
10.1254/JJP.86.203
Possible roles of cardiac chymase after myocardial infarction in hamster hearts.
D. Jin (2001)
10.1007/BF00177823
Genes for mast-cell serine protease and their molecular evolution
R. Huang (2004)
10.1016/S0014-2999(98)00343-4
The induction of a prolonged increase in microvascular permeability by human mast cell chymase.
S. He (1998)
10.1093/NAR/20.SUPPL.2019
The SWISS-PROT protein sequence data bank.
A. Bairoch (1992)
10.1016/S0014-5793(97)00752-7
Induction of chymase that forms angiotensin II in the monkey atherosclerotic aorta
S. Takai (1997)
10.1016/s0021-9258(19)70161-6
Susceptibility of soluble and matrix fibronectins to degradation by tissue proteinases, mast cell chymase and cathepsin G.
T. Vartio (1981)
10.1016/s0021-9258(18)98788-0
Structure, chromosomal assignment, and deduced amino acid sequence of a human gene for mast cell chymase.
G. Caughey (1991)
10.1021/BI00473A024
Dog mast cell chymase: molecular cloning and characterization.
G. Caughey (1990)
10.1074/jbc.272.11.7127
Cleavage of Type I Procollagen by Human Mast Cell Chymase Initiates Collagen Fibril Formation and Generates a Unique Carboxyl-terminal Propeptide*
M. Kofford (1997)
Mast Cell Proteases in Immunology and Biology
G. Caughey (1995)
10.1111/J.1432-1033.1993.TB18316.X
Sites of nidogen cleavage by proteases involved in tissue homeostasis and remodelling.
U. Mayer (1993)
10.1016/s0021-9258(18)34171-1
Rapid conversion of angiotensin I to angiotensin II by neutrophil and mast cell proteinases.
C. Reilly (1982)
10.1016/s0021-9258(18)50690-6
Mapping the extended substrate binding site of cathepsin G and human leukocyte elastase. Studies with peptide substrates related to the alpha 1-protease inhibitor reactive site.
K. Nakajima (1979)



This paper is referenced by
10.1074/jbc.M511154200
Mast Cell and Neutrophil Peptidases Attack an Inactivation Segment in Hepatocyte Growth Factor to Generate NK4-like Antagonists*
W. Raymond (2006)
10.1016/j.molimm.2008.01.012
Extended cleavage specificity of mMCP-1, the major mucosal mast cell protease in mouse-high specificity indicates high substrate selectivity.
M. Andersson (2008)
10.4049/jimmunol.1002292
How Immune Peptidases Change Specificity: Cathepsin G Gained Tryptic Function but Lost Efficiency during Primate Evolution
W. Raymond (2010)
10.1016/j.jaci.2019.02.004
Regulation of the pleiotropic effects of tissue-resident mast cells.
M. Huber (2019)
10.1111/J.1472-9725.2004.00041.X
Genetic insights into mast cell chymase and tryptase function
G. Caughey (2004)
10.1172/JCI46139
Mast cell chymase reduces the toxicity of Gila monster venom, scorpion venom, and vasoactive intestinal polypeptide in mice.
Mitsuteru Akahoshi (2011)
10.1111/j.1476-5381.2012.02055.x
Chymase inhibition as a pharmacological target: a role in inflammatory and functional gastrointestinal disorders?
S. Heuston (2012)
Biological function of mast cell chymase
E. Chugunova (2004)
Expressão e caracterização das quimases recombinantes específicas de mastócitos de camundongos (mMCP4 e 5)
Programa de Pós-graduação (2014)
10.1016/j.febslet.2005.08.056
Differences between human proteinase 3 and neutrophil elastase and their murine homologues are relevant for murine model experiments
Olaf Wiesner (2005)
10.1016/J.MOLIMM.2007.10.015
Extended substrate specificity of opossum chymase--implications for the origin of mast cell chymases.
J. Reimer (2008)
10.1093/intimm/dxs081
Extended cleavage specificity of the mast cell chymase from the crab-eating macaque (Macaca fascicularis): an interesting animal model for the analysis of the function of the human mast cell chymase.
M. Thorpe (2012)
10.1073/pnas.1005758108
Essential role for mast cell tryptase in acute experimental colitis
M. Hamilton (2010)
Peripheral Regulation of Pain and Itch
ELÍN INGIBJÖRG (2019)
10.1016/B978-0-12-800267-4.00006-7
Development of mast cells and importance of their tryptase and chymase serine proteases in inflammation and wound healing.
Jeffrey Douaiher (2014)
10.1016/J.MOLIMM.2006.04.019
The expression pattern of three mast cell specific proteases during mouse development.
D. Abraham (2007)
10.1093/intimm/dxq021
The extended substrate recognition profile of the dog mast cell chymase reveals similarities and differences to the human chymase.
Maike Gallwitz (2010)
10.1093/intimm/dxn128
The extended substrate specificity of the human mast cell chymase reveals a serine protease with well-defined substrate recognition profile.
M. Andersson (2009)
10.1074/jbc.M301512200
Extended Substrate Specificity of Rat Mast Cell Protease 5, a Rodent α-Chymase with Elastase-like Primary Specificity*
U. Karlson (2003)
10.1182/blood-2010-01-257287
Mast cell proteases: multifaceted regulators of inflammatory disease.
G. Pejler (2010)
10.1084/jem.20030671
The Chymase, Mouse Mast Cell Protease 4, Constitutes the Major Chymotrypsin-like Activity in Peritoneum and Ear Tissue. A Role for Mouse Mast Cell Protease 4 in Thrombin Regulation and Fibronectin Turnover
E. Tchougounova (2003)
10.4049/jimmunol.1002803
The Inflammatory Response after an Epidermal Burn Depends on the Activities of Mouse Mast Cell Proteases 4 and 5
G. Younan (2010)
10.1016/B978-0-12-382219-2.00590-1
Chapter 590 – Chymases
G. Caughey (2013)
10.1016/j.kint.2019.08.037
Mast cell chymase protects against acute ischemic kidney injury by limiting neutrophil hyperactivation and recruitment.
L. C. Madjene (2019)
10.1172/JCI39345
Mast cell chymase limits the cardiac efficacy of Ang I-converting enzyme inhibitor therapy in rodents.
Chih-Chang Wei (2010)
10.1007/s00251-007-0202-1
Expression profile of novel members of the rat mast cell protease (rMCP)-2 and (rMCP)-8 families, and functional analyses of mouse mast cell protease (mMCP)-8
Maike Gallwitz (2007)
10.1073/pnas.0906372106
Mast cells regulate homeostatic intestinal epithelial migration and barrier function by a chymase/Mcpt4-dependent mechanism
K. Groschwitz (2009)
10.1081/RRS-200054355
Species Differences in Angiotensin II Generation and Degradation by Mast Cell Chymases
Y. Kunori (2005)
Biological Function of Mast Cell Chymase In vitro and in vivo studies: a thorny pathway
E. Chugunova (2004)
10.1016/j.ejphar.2015.04.045
Mast cell proteases as pharmacological targets.
G. Caughey (2016)
10.1371/journal.pone.0143091
Granule Associated Serine Proteases of Hematopoietic Cells – An Analysis of Their Appearance and Diversification during Vertebrate Evolution
Srinivas Akula (2015)
10.1016/j.dci.2018.11.019
Extended cleavage specificity of sheep mast cell protease‐2: A classical chymase with preference to aromatic P1 substrate residues
Zhirong Fu (2019)
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