7pck
From Proteopedia
(New page: 200px<br /> <applet load="7pck" size="450" color="white" frame="true" align="right" spinBox="true" caption="7pck, resolution 3.2Å" /> '''CRYSTAL STRUCTURE OF...) |
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| - | [[Image:7pck.gif|left|200px]]<br /> | + | [[Image:7pck.gif|left|200px]]<br /><applet load="7pck" size="350" color="white" frame="true" align="right" spinBox="true" |
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caption="7pck, resolution 3.2Å" /> | caption="7pck, resolution 3.2Å" /> | ||
'''CRYSTAL STRUCTURE OF WILD TYPE HUMAN PROCATHEPSIN K'''<br /> | '''CRYSTAL STRUCTURE OF WILD TYPE HUMAN PROCATHEPSIN K'''<br /> | ||
==Overview== | ==Overview== | ||
| - | Cathepsin K is a lysosomal cysteine protease belonging to the papain | + | Cathepsin K is a lysosomal cysteine protease belonging to the papain superfamily. It has been implicated as a major mediator of osteoclastic bone resorption. Wild-type human procathepsin K has been crystallized in a glycosylated and a deglycosylated form. The latter crystals diffract better, to 3.2 A resolution, and contain four molecules in the asymmetric unit. The structure was solved by molecular replacement and refined to an R-factor of 0.194. The N-terminal fragment of the proregion forms a globular domain while the C-terminal segment is extended and shows substantial flexibility. The proregion interacts with the enzyme along the substrate binding groove and along the proregion binding loop (residues Ser138-Asn156). It binds to the active site in the opposite direction to that of natural substrates. The overall binding mode of the proregion to cathepsin K is similar to that observed in cathepsin L, caricain, and cathepsin B, but there are local differences that likely contribute to the specificity of these proregions for their cognate enzymes. The main observed difference is in the position of the short helix alpha3p (67p-75p), which occupies the S' subsites. As in the other proenzymes, the proregion utilizes the S2 subsite for anchoring by placing a leucine side chain there, according to the specificity of cathepsin K toward its substrate. |
==Disease== | ==Disease== | ||
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==About this Structure== | ==About this Structure== | ||
| - | 7PCK is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Active as [http://en.wikipedia.org/wiki/Cathepsin_K Cathepsin K], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.22.38 3.4.22.38] Full crystallographic information is available from [http:// | + | 7PCK is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Active as [http://en.wikipedia.org/wiki/Cathepsin_K Cathepsin K], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.22.38 3.4.22.38] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7PCK OCA]. |
==Reference== | ==Reference== | ||
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[[Category: proregion]] | [[Category: proregion]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 19:17:30 2008'' |
Revision as of 17:17, 21 February 2008
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CRYSTAL STRUCTURE OF WILD TYPE HUMAN PROCATHEPSIN K
Contents |
Overview
Cathepsin K is a lysosomal cysteine protease belonging to the papain superfamily. It has been implicated as a major mediator of osteoclastic bone resorption. Wild-type human procathepsin K has been crystallized in a glycosylated and a deglycosylated form. The latter crystals diffract better, to 3.2 A resolution, and contain four molecules in the asymmetric unit. The structure was solved by molecular replacement and refined to an R-factor of 0.194. The N-terminal fragment of the proregion forms a globular domain while the C-terminal segment is extended and shows substantial flexibility. The proregion interacts with the enzyme along the substrate binding groove and along the proregion binding loop (residues Ser138-Asn156). It binds to the active site in the opposite direction to that of natural substrates. The overall binding mode of the proregion to cathepsin K is similar to that observed in cathepsin L, caricain, and cathepsin B, but there are local differences that likely contribute to the specificity of these proregions for their cognate enzymes. The main observed difference is in the position of the short helix alpha3p (67p-75p), which occupies the S' subsites. As in the other proenzymes, the proregion utilizes the S2 subsite for anchoring by placing a leucine side chain there, according to the specificity of cathepsin K toward its substrate.
Disease
Known disease associated with this structure: Pycnodysostosis OMIM:[601105]
About this Structure
7PCK is a Single protein structure of sequence from Homo sapiens. Active as Cathepsin K, with EC number 3.4.22.38 Full crystallographic information is available from OCA.
Reference
Crystal structure of wild-type human procathepsin K., Sivaraman J, Lalumiere M, Menard R, Cygler M, Protein Sci. 1999 Feb;8(2):283-90. PMID:10048321
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