2djg: Difference between revisions
New page: left|200px<br /> <applet load="2djg" size="450" color="white" frame="true" align="right" spinBox="true" caption="2djg, resolution 2.05Å" /> '''Re-refinement of th... |
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[[Image:2djg.gif|left|200px]]<br /> | [[Image:2djg.gif|left|200px]]<br /><applet load="2djg" size="350" color="white" frame="true" align="right" spinBox="true" | ||
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'''Re-refinement of the native structure of human dipeptidyl peptidase I (cathepsin C)'''<br /> | '''Re-refinement of the native structure of human dipeptidyl peptidase I (cathepsin C)'''<br /> | ||
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==Overview== | ==Overview== | ||
hDDPI (human dipeptidyl peptidase I) is a lysosomal cysteine protease, involved in zymogen activation of granule-associated proteases, including, granzymes A and B from cytotoxic T-lymphocytes and natural killer cells, cathepsin G and neutrophil elastase, and mast cell tryptase and chymase., In the present paper, we provide the first crystal structure of an, hDPPI-inhibitor complex. The inhibitor Gly-Phe-CHN2 (Gly-Phe-diazomethane), was co-crystallized with hDPPI and the structure was determined at 2.0 A, (1 A=0.1 nm) resolution. The structure of the native enzyme was also, determined to 2.05 A resolution to resolve apparent discrepancies between, the complex structure and the previously published structure of the native, enzyme. The new structure of the native enzyme is, within the experimental, error, identical with the structure of the enzyme-inhibitor complex, presented here. The inhibitor interacts with three subunits of hDPPI, and, is covalently bound to Cys234 at the active site. The interaction between, the totally conserved Asp1 of hDPPI and the ammonium group of the, inhibitor forms an essential interaction that mimics enzyme-substrate, interactions. The structure of the inhibitor complex provides an, explanation of the substrate specificity of hDPPI, and gives a background, for the design of new inhibitors. | hDDPI (human dipeptidyl peptidase I) is a lysosomal cysteine protease, involved in zymogen activation of granule-associated proteases, including, granzymes A and B from cytotoxic T-lymphocytes and natural killer cells, cathepsin G and neutrophil elastase, and mast cell tryptase and chymase., In the present paper, we provide the first crystal structure of an, hDPPI-inhibitor complex. The inhibitor Gly-Phe-CHN2 (Gly-Phe-diazomethane), was co-crystallized with hDPPI and the structure was determined at 2.0 A, (1 A=0.1 nm) resolution. The structure of the native enzyme was also, determined to 2.05 A resolution to resolve apparent discrepancies between, the complex structure and the previously published structure of the native, enzyme. The new structure of the native enzyme is, within the experimental, error, identical with the structure of the enzyme-inhibitor complex, presented here. The inhibitor interacts with three subunits of hDPPI, and, is covalently bound to Cys234 at the active site. The interaction between, the totally conserved Asp1 of hDPPI and the ammonium group of the, inhibitor forms an essential interaction that mimics enzyme-substrate, interactions. The structure of the inhibitor complex provides an, explanation of the substrate specificity of hDPPI, and gives a background, for the design of new inhibitors. | ||
==About this Structure== | ==About this Structure== | ||
2DJG is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with NAG, CL and SO4 as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Dipeptidyl-peptidase_I Dipeptidyl-peptidase I], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.14.1 3.4.14.1] Full crystallographic information is available from [http:// | 2DJG is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=NAG:'>NAG</scene>, <scene name='pdbligand=CL:'>CL</scene> and <scene name='pdbligand=SO4:'>SO4</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Dipeptidyl-peptidase_I Dipeptidyl-peptidase I], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.14.1 3.4.14.1] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2DJG OCA]. | ||
==Reference== | ==Reference== | ||
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[[Category: cysteine protease]] | [[Category: cysteine protease]] | ||
[[Category: dipeptidyl peptidase i]] | [[Category: dipeptidyl peptidase i]] | ||
[[Category: hydrolase]] | |||
[[Category: re-refinement]] | [[Category: re-refinement]] | ||
''Page seeded by [http:// | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Jan 23 11:17:44 2008'' | ||
Revision as of 12:17, 23 January 2008
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Re-refinement of the native structure of human dipeptidyl peptidase I (cathepsin C)
OverviewOverview
hDDPI (human dipeptidyl peptidase I) is a lysosomal cysteine protease, involved in zymogen activation of granule-associated proteases, including, granzymes A and B from cytotoxic T-lymphocytes and natural killer cells, cathepsin G and neutrophil elastase, and mast cell tryptase and chymase., In the present paper, we provide the first crystal structure of an, hDPPI-inhibitor complex. The inhibitor Gly-Phe-CHN2 (Gly-Phe-diazomethane), was co-crystallized with hDPPI and the structure was determined at 2.0 A, (1 A=0.1 nm) resolution. The structure of the native enzyme was also, determined to 2.05 A resolution to resolve apparent discrepancies between, the complex structure and the previously published structure of the native, enzyme. The new structure of the native enzyme is, within the experimental, error, identical with the structure of the enzyme-inhibitor complex, presented here. The inhibitor interacts with three subunits of hDPPI, and, is covalently bound to Cys234 at the active site. The interaction between, the totally conserved Asp1 of hDPPI and the ammonium group of the, inhibitor forms an essential interaction that mimics enzyme-substrate, interactions. The structure of the inhibitor complex provides an, explanation of the substrate specificity of hDPPI, and gives a background, for the design of new inhibitors.
About this StructureAbout this Structure
2DJG is a Protein complex structure of sequences from Homo sapiens with , and as ligands. Active as Dipeptidyl-peptidase I, with EC number 3.4.14.1 Full crystallographic information is available from OCA.
ReferenceReference
The crystal structure of human dipeptidyl peptidase I (cathepsin C) in complex with the inhibitor Gly-Phe-CHN2., Molgaard A, Arnau J, Lauritzen C, Larsen S, Petersen G, Pedersen J, Biochem J. 2007 Feb 1;401(3):645-50. PMID:17020538
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