1mzd
From Proteopedia
(New page: 200px<br /> <applet load="1mzd" size="450" color="white" frame="true" align="right" spinBox="true" caption="1mzd, resolution 2.9Å" /> '''crystal structure of...) |
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| - | [[Image:1mzd.gif|left|200px]]<br /> | + | [[Image:1mzd.gif|left|200px]]<br /><applet load="1mzd" size="350" color="white" frame="true" align="right" spinBox="true" |
| - | <applet load="1mzd" size=" | + | |
caption="1mzd, resolution 2.9Å" /> | caption="1mzd, resolution 2.9Å" /> | ||
'''crystal structure of human pro-granzyme K'''<br /> | '''crystal structure of human pro-granzyme K'''<br /> | ||
==Overview== | ==Overview== | ||
| - | Granzyme K (GzmK) belongs to a family of trypsin-like serine proteases | + | Granzyme K (GzmK) belongs to a family of trypsin-like serine proteases localized in electron dense cytoplasmic granules of activated natural killer and cytotoxic T-cells. Like the related granzymes A and B, GzmK can trigger DNA fragmentation and is involved in apoptosis. We expressed the Ser(195) --> Ala variant of human pro-GzmK in Escherichia coli, crystallized it, and determined its 2.2-A x-ray crystal structure. Pro-GzmK possesses a surprisingly rigid structure, which is most similar to activated serine proteases, in particular complement factor D, and not their proforms. The N-terminal peptide Met(14)-Ile(17) projects freely into solution and can be readily approached by cathepsin C, the natural convertase of pro-granzymes. The pre-shaped S1 pocket is occupied by the ion paired residues Lys(188B)-Asp(194) and is hence not available for proper substrate binding. The Ser(214)-Cys(220) segment, which normally provides a template for substrate binding, bulges out of the active site and is distorted. With analogy to complement factor D, we suggest that this strand will maintain its non-productive conformation in mature GzmK, mainly due to the unusual residues Gly(215), Glu(219), and Val(94). We hypothesize that GzmK is proteolytically active only toward specific, as yet unidentified substrates, which upon approach transiently induce a functional active-site conformation. |
==About this Structure== | ==About this Structure== | ||
| - | 1MZD is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http:// | + | 1MZD is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1MZD OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Fuentes-Prior, P.]] | [[Category: Fuentes-Prior, P.]] | ||
[[Category: Hink-Schauer, C.]] | [[Category: Hink-Schauer, C.]] | ||
| - | [[Category: Jenne, D | + | [[Category: Jenne, D E.]] |
[[Category: Klinkert, W.]] | [[Category: Klinkert, W.]] | ||
[[Category: Wilharm, E.]] | [[Category: Wilharm, E.]] | ||
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[[Category: serine protease]] | [[Category: serine protease]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 14:00:33 2008'' |
Revision as of 12:00, 21 February 2008
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crystal structure of human pro-granzyme K
Overview
Granzyme K (GzmK) belongs to a family of trypsin-like serine proteases localized in electron dense cytoplasmic granules of activated natural killer and cytotoxic T-cells. Like the related granzymes A and B, GzmK can trigger DNA fragmentation and is involved in apoptosis. We expressed the Ser(195) --> Ala variant of human pro-GzmK in Escherichia coli, crystallized it, and determined its 2.2-A x-ray crystal structure. Pro-GzmK possesses a surprisingly rigid structure, which is most similar to activated serine proteases, in particular complement factor D, and not their proforms. The N-terminal peptide Met(14)-Ile(17) projects freely into solution and can be readily approached by cathepsin C, the natural convertase of pro-granzymes. The pre-shaped S1 pocket is occupied by the ion paired residues Lys(188B)-Asp(194) and is hence not available for proper substrate binding. The Ser(214)-Cys(220) segment, which normally provides a template for substrate binding, bulges out of the active site and is distorted. With analogy to complement factor D, we suggest that this strand will maintain its non-productive conformation in mature GzmK, mainly due to the unusual residues Gly(215), Glu(219), and Val(94). We hypothesize that GzmK is proteolytically active only toward specific, as yet unidentified substrates, which upon approach transiently induce a functional active-site conformation.
About this Structure
1MZD is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
Reference
The 2.2-A crystal structure of human pro-granzyme K reveals a rigid zymogen with unusual features., Hink-Schauer C, Estebanez-Perpina E, Wilharm E, Fuentes-Prior P, Klinkert W, Bode W, Jenne DE, J Biol Chem. 2002 Dec 27;277(52):50923-33. Epub 2002 Oct 15. PMID:12384499
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