View source for 2djg


==Re-determination of the native structure of human dipeptidyl peptidase I (cathepsin C)==
<StructureSection load='2djg' size='340' side='right' caption='[[2djg]], [[Resolution|resolution]] 2.05&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[2djg]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2DJG OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2DJG FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1k3b|1k3b]], [[1jqp|1jqp]], [[2djf|2djf]]</td></tr>
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">CTSC ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[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] </span></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2djg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2djg OCA], [http://pdbe.org/2djg PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2djg RCSB], [http://www.ebi.ac.uk/pdbsum/2djg PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2djg ProSAT]</span></td></tr>
</table>
== Disease ==
[[http://www.uniprot.org/uniprot/CATC_HUMAN CATC_HUMAN]] Defects in CTSC are a cause of Papillon-Lefevre syndrome (PLS) [MIM:[http://omim.org/entry/245000 245000]]; also known as keratosis palmoplantaris with periodontopathia. PLS is an autosomal recessive disorder characterized by palmoplantar keratosis and severe periodontitis affecting deciduous and permanent dentitions and resulting in premature tooth loss. The palmoplantar keratotic phenotype vary from mild psoriasiform scaly skin to overt hyperkeratosis. Keratosis also affects other sites such as elbows and knees.<ref>PMID:11180601</ref> <ref>PMID:12809647</ref> <ref>PMID:10581027</ref> <ref>PMID:10662808</ref> <ref>PMID:11106356</ref> <ref>PMID:11180012</ref> <ref>PMID:11886537</ref> <ref>PMID:11158173</ref> <ref>PMID:12112662</ref> <ref>PMID:14974080</ref> <ref>PMID:15108292</ref> <ref>PMID:15991336</ref>   Defects in CTSC are a cause of Haim-Munk syndrome (HMS) [MIM:[http://omim.org/entry/245010 245010]]; also known as keratosis palmoplantaris with periodontopathia and onychogryposis or Cochin Jewish disorder. HMS is an autosomal recessive disorder characterized by palmoplantar keratosis, onychogryphosis and periodontitis. Additional features are pes planus, arachnodactyly, and acroosteolysis.<ref>PMID:10662807</ref>   Defects in CTSC are a cause of aggressive periodontititis type 1 (AP1) [MIM:[http://omim.org/entry/170650 170650]]; also known as juvenile periodontitis (JPD) and prepubertal periodontitis (PPP). AP1 is characterized by severe and protracted gingival infections, leading to tooth loss. AP1 inheritance is autosomal dominant.<ref>PMID:10662808</ref> <ref>PMID:14974080</ref>  
== Function ==
[[http://www.uniprot.org/uniprot/CATC_HUMAN CATC_HUMAN]] Thiol protease. Has dipeptidylpeptidase activity. Active against a broad range of dipeptide substrates composed of both polar and hydrophobic amino acids. Proline cannot occupy the P1 position and arginine cannot occupy the P2 position of the substrate. Can act as both an exopeptidase and endopeptidase. Activates serine proteases such as elastase, cathepsin G and granzymes A and B. Can also activate neuraminidase and factor XIII.<ref>PMID:1586157</ref>  
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
Check<jmol>
  <jmolCheckbox>
    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/dj/2djg_consurf.spt"</scriptWhenChecked>
    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
    <text>to colour the structure by Evolutionary Conservation</text>
  </jmolCheckbox>
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=2djg ConSurf].
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
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.

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<ref>PMID:17020538</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 2djg" style="background-color:#fffaf0;"></div>

==See Also==
*[[Cathepsin|Cathepsin]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Dipeptidyl-peptidase I]]
[[Category: Human]]
[[Category: Arnau, J]]
[[Category: Larsen, S]]
[[Category: Lauritzen, C]]
[[Category: Molgaard, A]]
[[Category: Pedersen, J]]
[[Category: Petersen, G]]
[[Category: Cathepsin c]]
[[Category: Cysteine protease]]
[[Category: Dipeptidyl peptidase i]]
[[Category: Hydrolase]]
[[Category: Re-refinement]]