Evolution of Proteolytic Enzymes

Neurath, Hans

doi:10.1126/science.6369538

Cited by 632 publications

(407 citation statements)

References 76 publications

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“…Their activity depends on a catalytic triad consisting of residues Asp 102 , His 57 , and Ser 195 (chymotrypsin numbering), which are widely separated in the primary sequence but are brought together at the active site of the enzymes in their tertiary structures [9].…”

Section: Serine Proteinasesmentioning

confidence: 99%

The cell biology of leukocyte-mediated proteolysis

Owen

Campbell

1999

Journal of Leukocyte Biology

383

399

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Leukocyte-derived proteinases have the capacity to degrade every component of the extracellular matrix, and thereby play fundamental roles in physiological processes. However, if the activity of these proteinases is uncontrolled or dysregulated, they have the capacity to contribute to tissue injury that potentially affects every organ in the body. Although there is a substantial literature on structure and activity of these proteinases when they are free in solution, until recently there has been little information about the cell biology of proteinases and their inhibitors. Recent studies, however, have identified several mechanisms by which inflammatory cells can degrade extracellular proteins in a milieu that contains high-affinity proteinase inhibitors. J. Leukoc. Biol. 65: 137-150; 1999.

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Section: Serine Proteinasesmentioning

confidence: 99%

The cell biology of leukocyte-mediated proteolysis

Owen

Campbell

1999

Journal of Leukocyte Biology

383

399

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“…By the end of the 1980s there was an accepted system to classify endopeptidases on the basis of mechanism of action and three-dimensional structure (Neurath, 1989). Four mechanistic classes of proteases (serine, cysteine, aspartic, and metallo) were identified, and six families (two serine families: chymotrypsin and subtilisin; one cysteine: represented by papain; one aspartic: penicillopepsin; two metallo: carboxypeptidase and thermolysin families).…”

mentioning

confidence: 99%

The astacin family of metalloendopeptidases

1995

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The astacin family of metalloendopeptidases was recognized as a novel family of proteases in the 1990s. The crayfish enzyme astacin was the first characterized and is one of the smallest members of the family. More than 20 members of the family have now been identified. They have been detected in species ranging from hydra to humans, in mature and in developmental systems. Proposed functions of these proteases include activation of growth factors, degradation of polypeptides, and processing of extracellular proteins. Astacin family proteases are synthesized with NH,-terminal signal and proenzyme sequences, and many (such as meprins, BMP-1, folloid) contain multiple domains COOH-terminal to the protease domain. They are either secreted from cells or are plasma membrane-associated enzymes. They have some distinguishing features in addition to the signature sequence in the protease domain: HEXXHXXGFXHEXXRXDR. They have a unique type of zinc binding, with pentacoordination, and a protease domain tertiary structure that contains common attributes with serralysins, matrix metalloendopeptidases, and snake venom proteases; they cleave peptide bonds in polypeptides such as insulin B chain and bradykinin and in proteins such as casein and gelatin; and they have arylamidase activity. Meprins are unique proteases in the astacin family, and indeed in the animal kingdom, in their oligomeric structure; they are dimers of disulfide-linked dimers and are highly glycosylated, type I integral membrane proteins that have many attributes of receptors or integrins with adhesion, epidermal growth factor-like, and transmembrane domains. The 01 and /3 subunits are differentially expressed and processed to yield latent and active proteases as well as membraneassociated and secreted forms. Meprins represent excellent models of hetero-and homo-oligomeric enzymes that are regulated at the transcriptional and posttranslational levels.

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“…Proteinases play a central role in such basic physiological processes as posttranslational processing, fertilization, prohormone processing, complement activation, blood coagulation, and fibrinolysis [1]. Proteinases have also been implicated in certain diseases including trauma, tumor metastasis, emphysema, and arthritis [2].…”

Section: Introductionmentioning

confidence: 99%

Synthesis, cloning and expression in Escherichia coli of a gene coding for the Met8 → Leu CMTI I — a representative of the squash inhibitors of serine proteinases

et al. 1995

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A chemically synthesized gene coding for a Cucurbita maxima trypsin inhibitor modified at position P'3 (Met8--~ Leu CMTI I), i.e. at the third position downstream of the reactive site bond (ArgS-lle), was cloned into a derivative of the plasmid pAED4 that utilizes a T7 expression system. The gene was expressed in Escherichia coli as a fusion protein that accumulates in inclusion bodies. After reduction and CNBr cleavage of the fusion protein followed by oxidative refolding and reverse-phase HPLC, about 5 mg of pure protein was obtained per I of cell culture. Association constants of recombinant Leu-8-CMTI I with bovine ~l-trypsin and human cathepsin G are the same, within experimental error, as for CMTI I isolated from a natural source.

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Evolution of Proteolytic Enzymes

Cited by 632 publications

References 76 publications

The cell biology of leukocyte-mediated proteolysis

The cell biology of leukocyte-mediated proteolysis

The astacin family of metalloendopeptidases

Synthesis, cloning and expression in Escherichia coli of a gene coding for the Met8 → Leu CMTI I — a representative of the squash inhibitors of serine proteinases

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