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| {{STRUCTURE_1s4b| PDB=1s4b | SCENE= }} | | {{STRUCTURE_1s4b| PDB=1s4b | SCENE= }} |
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| '''Crystal structure of human thimet oligopeptidase.'''
| | ===Crystal structure of human thimet oligopeptidase.=== |
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| ==Overview==
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| Thimet oligopeptidase (TOP) is a zinc metallopeptidase that metabolizes a number of bioactive peptides and degrades peptides released by the proteasome, limiting antigenic presentation by MHC class I molecules. We present the crystal structure of human TOP at 2.0-A resolution. The active site is located at the base of a deep channel that runs the length of the elongated molecule, an overall fold first seen in the closely related metallopeptidase neurolysin. Comparison of the two related structures indicates hinge-like flexibility and identifies elements near one end of the channel that adopt different conformations. Relatively few of the sequence differences between TOP and neurolysin map to the proposed substrate-binding site, and four of these variable residues may account for differences in substrate specificity. In addition, a loop segment (residues 599-611) in TOP differs in conformation and degree of order from the corresponding neurolysin loop, suggesting it may also play a role in activity differences. Cysteines thought to mediate covalent oligomerization of rat TOP, which can inactivate the enzyme, are found to be surface-accessible in the human enzyme, and additional cysteines (residues 321,350, and 644) may also mediate multimerization in the human homolog. Disorder in the N terminus of TOP indicates it may be involved in subcellular localization, but a potential nuclear import element is found to be part of a helix and, therefore, unlikely to be involved in transport. A large acidic patch on the surface could potentially mediate a protein-protein interaction, possibly through formation of a covalent linkage.
| | The line below this paragraph, {{ABSTRACT_PUBMED_14998993}}, adds the Publication Abstract to the page |
| | (as it appears on PubMed at http://www.pubmed.gov), where 14998993 is the PubMed ID number. |
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| | {{ABSTRACT_PUBMED_14998993}} |
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| ==About this Structure== | | ==About this Structure== |
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| [[Category: Rodgers, D W.]] | | [[Category: Rodgers, D W.]] |
| [[Category: Zinc metallopeptidase domain]] | | [[Category: Zinc metallopeptidase domain]] |
| ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 08:16:43 2008'' | | |
| | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Jul 27 22:40:41 2008'' |