Wikipedia preview

出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2014/07/02 15:50:50」(JST)

wiki en

Carboxypeptidase A, from bovine pancreas

A carboxypeptidase (EC number 3.4.16 - 3.4.18) is a protease enzyme that hydrolyzes (cleaves) a peptide bond at the carboxy-terminal (C-terminal) end of a protein or peptide. (Contrast with an aminopeptidase, which cleaves peptide bonds at the other end of the protein.) Humans, animals, and plants contain several types of carboxypeptidases that have diverse functions ranging from catabolism to protein maturation.

Functions

The first carboxypeptidases studied were those involved in the digestion of food (pancreatic carboxypeptidases A1, A2, and B). However, most of the known carboxypeptidases are not involved in catabolism; they help to mature proteins (e.g., Post-translational modification) or regulate biological processes. For example, the biosynthesis of neuroendocrine peptides such as insulin requires a carboxypeptidase. Carboxypeptidases also function in blood clotting, growth factor production, wound healing, reproduction, and many other processes.

Classification

By active site mechanism

Carboxypeptidases are usually classified into one of several families based on their active site mechanism.

Enzymes that use a metal in the active site are called "metallo-carboxypeptidases" (EC number 3.4.17).
Other carboxypeptidases that use active site serine residues are called "serine carboxypeptidases" (EC number 3.4.16).
Those that use an active site cysteine are called "cysteine carboxypeptidase" (or "thiol carboxypeptidases")(EC number 3.4.18).

These names do not refer to the selectivity of the amino acid that is cleaved.

By substrate preference

Another classification system for carboxypeptidases refers to their substrate preference.

In this classification system, carboxypeptidases that have a stronger preference for those amino acids containing aromatic or branched hydrocarbon chains are called carboxypeptidase A (A for aromatic/aliphatic).
Carboxypeptidases that cleave positively charged amino acids (arginine, lysine) are called carboxypeptidase B (B for basic).

A metallo-carboxypeptidase that cleaves a C-terminal glutamate from the peptide N-acetyl-L-aspartyl-L-glutamate is called "glutamate carboxypeptidase".

A serine carboxypeptidase that cleaves the C-terminal residue from peptides containing the sequence -Pro-Xaa (Pro is proline, Xaa is any amino acid on the C-terminus of a peptide) is called "prolyl carboxypeptidase".

Activation

Some, but not all, carboxypeptidases are initially produced in an inactive form; this precursor form is referred to as a procarboxypeptidase. In the case of pancreatic carboxypeptidase A, the inactive zymogen form - pro-carboxypeptidase A - is converted to its active form - carboxypeptidase A - by the enzyme enteropeptidase. This mechanism ensures that the cells wherein pro-carboxypeptidase A is produced are not themselves digested.

External links

Carboxypeptidases at the US National Library of Medicine Medical Subject Headings (MeSH)
Protease section Stryer book '02

UpToDate Contents

全文を閲覧するには購読必要です。 To read the full text you will need to subscribe.

1. 高用量メトトレキサートの治療使用および毒性 therapeutic use and toxicity of high dose methotrexate
2. アナフィラキシーの臨床診断を裏付ける臨床検査 laboratory tests to support the clinical diagnosis of anaphylaxis
3. 肥満細胞由来のメディエーター mast cell derived mediators
4. 肥満細胞：増殖・分化、識別、および生理学的役割 mast cells development identification and physiologic roles
5. 補体系の制御因子および受容体 regulators and receptors of the complement system

English Journal

Carboxypeptidase M augments kinin B1 receptor signaling by conformational crosstalk and enhances endothelial nitric oxide output.

Zhang X, Tan F, Brovkovych V, Zhang Y, Lowry JL, Skidgel RA.AbstractAbstract The G protein-coupled receptors (GPCRs) are the largest class of membrane proteins that play key roles in transducing extracellular signals to intracellular proteins to generate cellular responses. The kinin GPCRs, named B1 (B1R) and B2 (B2R), are responsible for mediating the biological responses to kinin peptides released from the precursor kininogens. Bradykinin (BK) or kallidin (KD) are agonists for B2Rs, whereas their carboxypeptidase (CP)-generated metabolites, des-Arg9-BK or des-Arg10-KD, are specific agonists for B1Rs. Here, we review the evidence for a critical role of membrane-bound CPM in facilitating B1R signaling by its ability to directly activate the receptor via conformational crosstalk as well as generate its specific agonist. In endothelial cells, the CPM/B1R interaction facilitates B1R-dependent high-output nitric oxide under inflammatory conditions.
Biological chemistry.Biol Chem.2013 Mar 1;394(3):335-45. doi: 10.1515/hsz-2012-0290.
Abstract The G protein-coupled receptors (GPCRs) are the largest class of membrane proteins that play key roles in transducing extracellular signals to intracellular proteins to generate cellular responses. The kinin GPCRs, named B1 (B1R) and B2 (B2R), are responsible for mediating the biological re
PMID 23183746

The potential of carboxypeptidase M as a therapeutic target in cancer.

Denis CJ, Lambeir AM.SourceUniversity of Antwerp, Pharmaceutical Sciences, Laboratory of Medical Biochemistry , Universiteitsplein 1, Antwerp, B-2610 , Belgium +32 3 2652549 ; +32 3 2652685 ; anne-marie.lambeir@ua.ac.be.
Expert opinion on therapeutic targets.Expert Opin Ther Targets.2013 Mar;17(3):265-79. doi: 10.1517/14728222.2012.741122. Epub 2013 Jan 7.
Introduction: In the recent literature, carboxypeptidase M (CPM) emerged as a potential cancer biomarker. CPM modulates receptor signaling of kinins, anaphylatoxins, and chemokines. These CPM substrates affect proliferation, angiogenesis, and apoptosis of cancer cells. What is the evidence that CPM
PMID 23294303

Association of glutamate carboxypeptidase II (GCPII) haplotypes with breast and prostate cancer risk.

Divyya S, Naushad SM, Addlagatta A, Murthy PV, Reddy ChR, Digumarti RR, Gottumukkala SR, Subbarao SA, Kutala VK.SourceDepartment of Clinical Pharmacology & Therapeutics, Nizam's Institute of Medical Sciences, India.
Gene.Gene.2013 Mar 1;516(1):76-81. doi: 10.1016/j.gene.2012.11.047. Epub 2012 Dec 22.
In view of the pivotal role of glutamate carboxypeptidase II (GCPII) in carcinogenesis, its expression as prostate specific membrane antigen (PSMA) and folate hydrolase (FOLH1) may be influenced by its haplotypes, contributing to the etiology of prostate and breast cancer. To test this hypothesis, b
PMID 23266799

Japanese Journal

トリレオウイルスの蛋白質分解酵素処理による感染価上昇

高瀬公三,直原良子,岩瀬夏代,山崎憲一,小尾岳,タカセコウゾウ,ジキハラリョウコ,イワセナツヨ,ヤマザキケンイチ,オビタケシ,TAKASE Kozo,JIKIHARA Ryoko,IWASE Natsuyo,YAMAZAKI Kenichi,OBI Takesi
鹿兒島大學農學部學術報告=Bulletin of the Faculty of Agriculture, Kagoshima University 62, 59-64, 2012-03-31
… However, papain, carboxypeptidase and thrombin were not effective. …
NAID 120004140099

自然界から分離した黄麹菌(Aspergillus oryzae)と醸造用黄麹菌の比較解析

阿部真紀,小針清子,秋田修
実践女子大学生活科学部紀要 49, 7-14, 2012-03-10
… The activities of enzymes such as α-amylase, glucoamylase, acid carboxypeptidase, acid protease and neutral protease in rice kojiprepared by isolated eight strains and commercial strains were analyzed. …
NAID 110008916571

Related Pictures

★リンクテーブル★

リンク元	「カルボキシペプチダーゼ」
拡張検索	「serine-type D-Ala-D-Ala carboxypeptidase」「lysine carboxypeptidase」「procarboxypeptidase A」「carboxypeptidase B」「carboxypeptidase U」