2djf
From Proteopedia
(New page: 200px<br /> <applet load="2djf" size="450" color="white" frame="true" align="right" spinBox="true" caption="2djf, resolution 2.00Å" /> '''Crystal Structure o...) |
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caption="2djf, resolution 2.00Å" /> | caption="2djf, resolution 2.00Å" /> | ||
'''Crystal Structure of human dipeptidyl peptidase I (Cathepsin C) in complex with the inhibitor Gly-Phe-CHN2'''<br /> | '''Crystal Structure of human dipeptidyl peptidase I (Cathepsin C) in complex with the inhibitor Gly-Phe-CHN2'''<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. | ||
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| - | ==Disease== | ||
| - | Known diseases associated with this structure: Haim-Munk syndrome OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=602365 602365]], Papillon-Lefevre syndrome OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=602365 602365]], Periodontitis, juvenile OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=602365 602365]] | ||
==About this Structure== | ==About this Structure== | ||
| - | 2DJF 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, GLY, PHE, CH2 and ACY 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:// | + | 2DJF 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>, <scene name='pdbligand=GLY:'>GLY</scene>, <scene name='pdbligand=PHE:'>PHE</scene>, <scene name='pdbligand=CH2:'>CH2</scene> and <scene name='pdbligand=ACY:'>ACY</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=2DJF OCA]. |
==Reference== | ==Reference== | ||
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[[Category: covalently bound inhibitor]] | [[Category: covalently bound inhibitor]] | ||
[[Category: dppi-inhibitor complex]] | [[Category: dppi-inhibitor complex]] | ||
| + | [[Category: hydrolase]] | ||
[[Category: protein-inhibitor complex]] | [[Category: protein-inhibitor complex]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Jan 23 11:17:42 2008'' |
Revision as of 09:17, 23 January 2008
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Crystal Structure of human dipeptidyl peptidase I (Cathepsin C) in complex with the inhibitor Gly-Phe-CHN2
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.
About this Structure
2DJF 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.
Reference
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
Page seeded by OCA on Wed Jan 23 11:17:42 2008
Categories: Dipeptidyl-peptidase I | Homo sapiens | Protein complex | Arnau, J. | Larsen, S. | Lauritzen, C. | Molgaard, A. | Pedersen, J. | Petersen, G. | ACY | CH2 | CL | GLY | NAG | PHE | Cathepsin c inhibitor complex | Covalently bound inhibitor | Dppi-inhibitor complex | Hydrolase | Protein-inhibitor complex
