1fq3
From Proteopedia
(New page: 200px<br /> <applet load="1fq3" size="450" color="white" frame="true" align="right" spinBox="true" caption="1fq3, resolution 3.1Å" /> '''CRYSTAL STRUCTURE OF...) |
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| - | [[Image:1fq3.gif|left|200px]]<br /> | + | [[Image:1fq3.gif|left|200px]]<br /><applet load="1fq3" size="350" color="white" frame="true" align="right" spinBox="true" |
| - | <applet load="1fq3" size=" | + | |
caption="1fq3, resolution 3.1Å" /> | caption="1fq3, resolution 3.1Å" /> | ||
'''CRYSTAL STRUCTURE OF HUMAN GRANZYME B'''<br /> | '''CRYSTAL STRUCTURE OF HUMAN GRANZYME B'''<br /> | ||
==Overview== | ==Overview== | ||
| - | Granzyme B is the prototypic member of the granzymes, a family of | + | Granzyme B is the prototypic member of the granzymes, a family of trypsin-like serine proteinases localized in the dense cytoplasmic granules of activated natural killer cells and cytotoxic T lymphocytes. Granzyme B directly triggers apoptosis in target cells by activating the caspase pathway, and has been implicated in the etiology of rheumatoid arthritis. Human granzyme B expressed in a baculovirus system has been crystallized without inhibitor and its structure has been determined to 3.1 A resolution, after considerably improving the diffraction power of the crystals by controlled humidity changes. The granzyme B structure reveals an overall fold similar to that found in cathepsin G and human chymase. The guanidinium group of Arg226, anchored at the back of the S1-specificity pocket, can form a salt bridge with the P1-Asp side chain of a bound peptide substrate. The architecture of the substrate binding site of granzyme B appears to be designed to accommodate and cleave hexapeptides such as the sequence Ile-Glu-Thr-Asp-/Ser-Gly present in the activation site of pro-caspase-3, a proven physiological substrate of granzyme B. These granzyme B crystals, with fully accessible active sites, are well suited for soaking with small synthetic inhibitors that might be used for a treatment of chronic inflammatory disorders. |
==About this Structure== | ==About this Structure== | ||
| - | 1FQ3 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with SO4 as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [http://en.wikipedia.org/wiki/Granzyme_B Granzyme B], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.21.79 3.4.21.79] Full crystallographic information is available from [http:// | + | 1FQ3 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=SO4:'>SO4</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [http://en.wikipedia.org/wiki/Granzyme_B Granzyme B], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.21.79 3.4.21.79] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1FQ3 OCA]. |
==Reference== | ==Reference== | ||
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[[Category: chymotrypsin-like serine proteinase]] | [[Category: chymotrypsin-like serine proteinase]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 12:41:24 2008'' |
Revision as of 10:41, 21 February 2008
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CRYSTAL STRUCTURE OF HUMAN GRANZYME B
Overview
Granzyme B is the prototypic member of the granzymes, a family of trypsin-like serine proteinases localized in the dense cytoplasmic granules of activated natural killer cells and cytotoxic T lymphocytes. Granzyme B directly triggers apoptosis in target cells by activating the caspase pathway, and has been implicated in the etiology of rheumatoid arthritis. Human granzyme B expressed in a baculovirus system has been crystallized without inhibitor and its structure has been determined to 3.1 A resolution, after considerably improving the diffraction power of the crystals by controlled humidity changes. The granzyme B structure reveals an overall fold similar to that found in cathepsin G and human chymase. The guanidinium group of Arg226, anchored at the back of the S1-specificity pocket, can form a salt bridge with the P1-Asp side chain of a bound peptide substrate. The architecture of the substrate binding site of granzyme B appears to be designed to accommodate and cleave hexapeptides such as the sequence Ile-Glu-Thr-Asp-/Ser-Gly present in the activation site of pro-caspase-3, a proven physiological substrate of granzyme B. These granzyme B crystals, with fully accessible active sites, are well suited for soaking with small synthetic inhibitors that might be used for a treatment of chronic inflammatory disorders.
About this Structure
1FQ3 is a Single protein structure of sequence from Homo sapiens with as ligand. Active as Granzyme B, with EC number 3.4.21.79 Full crystallographic information is available from OCA.
Reference
Crystal structure of the caspase activator human granzyme B, a proteinase highly specific for an Asp-P1 residue., Estebanez-Perpina E, Fuentes-Prior P, Belorgey D, Braun M, Kiefersauer R, Maskos K, Huber R, Rubin H, Bode W, Biol Chem. 2000 Dec;381(12):1203-14. PMID:11209755
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