2djf

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{{STRUCTURE_2djf| PDB=2djf | SCENE= }}
{{STRUCTURE_2djf| PDB=2djf | SCENE= }}
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'''Crystal Structure of human dipeptidyl peptidase I (Cathepsin C) in complex with the inhibitor Gly-Phe-CHN2'''
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===Crystal Structure of human dipeptidyl peptidase I (Cathepsin C) in complex with the inhibitor Gly-Phe-CHN2===
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==Overview==
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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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(as it appears on PubMed at http://www.pubmed.gov), where 17020538 is the PubMed ID number.
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==Disease==
==Disease==
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[[Category: Hydrolase]]
[[Category: Hydrolase]]
[[Category: Protein-inhibitor complex]]
[[Category: Protein-inhibitor complex]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Tue Jul 29 13:41:50 2008''

Revision as of 10:41, 29 July 2008

Image:2djf.png

Template:STRUCTURE 2djf

Contents

Crystal Structure of human dipeptidyl peptidase I (Cathepsin C) in complex with the inhibitor Gly-Phe-CHN2

Template:ABSTRACT PUBMED 17020538

Disease

Known disease associated with this structure: Haim-Munk syndrome OMIM:[602365], Papillon-Lefevre syndrome OMIM:[602365], Periodontitis, juvenile OMIM:[602365]

About this Structure

2DJF is a Protein complex structure of sequences from Homo sapiens. 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

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