1s4b: Difference between revisions

Revision as of 08:16, 3 May 2008

Crystal structure of human thimet oligopeptidase.

OverviewOverview

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.

About this StructureAbout this Structure

1S4B is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.

ReferenceReference

Crystal structure of human thimet oligopeptidase provides insight into substrate recognition, regulation, and localization., Ray K, Hines CS, Coll-Rodriguez J, Rodgers DW, J Biol Chem. 2004 May 7;279(19):20480-9. Epub 2004 Mar 3. PMID:14998993 Page seeded by OCA on Sat May 3 08:16:43 2008

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OCA

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 [[Image:1s4b.gif|left|200px]]
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-|ACTIVITY= <span class='plainlinks'>[http://en.wikipedia.org/wiki/Thimet_oligopeptidase Thimet oligopeptidase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.24.15 3.4.24.15] </span>
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-}}
 '''Crystal structure of human thimet oligopeptidase.'''
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 [[Category: Ray, K.]]
 [[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 Mar 30 23:37:07 2008''