1pci: Difference between revisions
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==Overview== | ==Overview== | ||
BACKGROUND: Cysteine proteases are involved in a variety of cellular, processes including cartilage degradation in arthritis, the progression of, Alzheimer's disease and cancer invasion: these enzymes are therefore of, immense biological importance. Caricain is the most basic of the cysteine, proteases found in the latex of Carica papaya. It is a member of the, papain superfamily and is homologous to other plant and animal cysteine, proteases. Caricain is naturally expressed as an inactive zymogen called, procaricain. The inactive form of the protease contains an inhibitory, proregion which consists of an additional 106 N-terminal amino acids; the, proregion is removed upon activation. RESULTS: The crystal structure of, procaricain has been refined to 3.2 A resolution; the final model ... | BACKGROUND: Cysteine proteases are involved in a variety of cellular, processes including cartilage degradation in arthritis, the progression of, Alzheimer's disease and cancer invasion: these enzymes are therefore of, immense biological importance. Caricain is the most basic of the cysteine, proteases found in the latex of Carica papaya. It is a member of the, papain superfamily and is homologous to other plant and animal cysteine, proteases. Caricain is naturally expressed as an inactive zymogen called, procaricain. The inactive form of the protease contains an inhibitory, proregion which consists of an additional 106 N-terminal amino acids; the, proregion is removed upon activation. RESULTS: The crystal structure of, procaricain has been refined to 3.2 A resolution; the final model consists, of three non-crystallographically related molecules. The proregion of, caricain forms a separate globular domain which binds to the C-terminal, domain of mature caricain. The proregion also contains an extended, polypeptide chain which runs through the substrate-binding cleft, in the, opposite direction to that of the substrate, and connects to the N, terminus of the mature region. The mature region does not undergo any, conformational change on activation. CONCLUSIONS: We conclude that the, rate-limiting step in the in vitro activation of procaricain is the, dissociation of the prodomain, which is then followed by proteolytic, cleavage of the extended polypeptide chain of the proregion. The prodomain, provides a stable scaffold which may facilitate the folding of the, C-terminal lobe of procaricain. | ||
==About this Structure== | ==About this Structure== | ||
1PCI is a | 1PCI is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Carica_papaya Carica papaya]. Active as [http://en.wikipedia.org/wiki/Chymopapain Chymopapain], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.22.6 3.4.22.6] Structure known Active Sites: ACA, ACB and ACC. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1PCI OCA]. | ||
==Reference== | ==Reference== | ||
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[[Category: zymogen]] | [[Category: zymogen]] | ||
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Revision as of 13:24, 5 November 2007
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PROCARICAIN
OverviewOverview
BACKGROUND: Cysteine proteases are involved in a variety of cellular, processes including cartilage degradation in arthritis, the progression of, Alzheimer's disease and cancer invasion: these enzymes are therefore of, immense biological importance. Caricain is the most basic of the cysteine, proteases found in the latex of Carica papaya. It is a member of the, papain superfamily and is homologous to other plant and animal cysteine, proteases. Caricain is naturally expressed as an inactive zymogen called, procaricain. The inactive form of the protease contains an inhibitory, proregion which consists of an additional 106 N-terminal amino acids; the, proregion is removed upon activation. RESULTS: The crystal structure of, procaricain has been refined to 3.2 A resolution; the final model consists, of three non-crystallographically related molecules. The proregion of, caricain forms a separate globular domain which binds to the C-terminal, domain of mature caricain. The proregion also contains an extended, polypeptide chain which runs through the substrate-binding cleft, in the, opposite direction to that of the substrate, and connects to the N, terminus of the mature region. The mature region does not undergo any, conformational change on activation. CONCLUSIONS: We conclude that the, rate-limiting step in the in vitro activation of procaricain is the, dissociation of the prodomain, which is then followed by proteolytic, cleavage of the extended polypeptide chain of the proregion. The prodomain, provides a stable scaffold which may facilitate the folding of the, C-terminal lobe of procaricain.
About this StructureAbout this Structure
1PCI is a Single protein structure of sequence from Carica papaya. Active as Chymopapain, with EC number 3.4.22.6 Structure known Active Sites: ACA, ACB and ACC. Full crystallographic information is available from OCA.
ReferenceReference
The prosequence of procaricain forms an alpha-helical domain that prevents access to the substrate-binding cleft., Groves MR, Taylor MA, Scott M, Cummings NJ, Pickersgill RW, Jenkins JA, Structure. 1996 Oct 15;4(10):1193-203. PMID:8939744
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