2djg: Difference between revisions

Revision as of 09:54, 11 September 2015

Re-determination of the native structure of human dipeptidyl peptidase I (cathepsin C)Re-determination of the native structure of human dipeptidyl peptidase I (cathepsin C)

Structural highlights

2djg is a 3 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	, , ,
Related:	1k3b, 1jqp, 2djf
Gene:	CTSC (HUMAN)
Activity:	Dipeptidyl-peptidase I, with EC number 3.4.14.1
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum

Disease

[CATC_HUMAN] Defects in CTSC are a cause of Papillon-Lefevre syndrome (PLS) [MIM: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.^[1] ^[2] ^[3] ^[4] ^[5] ^[6] ^[7] ^[8] ^[9] ^[10] ^[11] ^[12] Defects in CTSC are a cause of Haim-Munk syndrome (HMS) [MIM: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.^[13] Defects in CTSC are a cause of aggressive periodontititis type 1 (AP1) [MIM: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.^[14] ^[15]

Function

[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.^[16]

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

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^[17]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Allende LM, Garcia-Perez MA, Moreno A, Corell A, Carasol M, Martinez-Canut P, Arnaiz-Villena A. Cathepsin C gene: First compound heterozygous patient with Papillon-Lefevre syndrome and a novel symptomless mutation. Hum Mutat. 2001 Feb;17(2):152-3. PMID:11180601 doi:<152::AID-HUMU10>3.0.CO;2-# 10.1002/1098-1004(200102)17:2<152::AID-HUMU10>3.0.CO;2-#
↑ Allende LM, Moreno A, de Unamuno P. A genetic study of cathepsin C gene in two families with Papillon-Lefevre syndrome. Mol Genet Metab. 2003 Jun;79(2):146-8. PMID:12809647
↑ Toomes C, James J, Wood AJ, Wu CL, McCormick D, Lench N, Hewitt C, Moynihan L, Roberts E, Woods CG, Markham A, Wong M, Widmer R, Ghaffar KA, Pemberton M, Hussein IR, Temtamy SA, Davies R, Read AP, Sloan P, Dixon MJ, Thakker NS. Loss-of-function mutations in the cathepsin C gene result in periodontal disease and palmoplantar keratosis. Nat Genet. 1999 Dec;23(4):421-4. PMID:10581027 doi:10.1038/70525
↑ Hart TC, Hart PS, Michalec MD, Zhang Y, Marazita ML, Cooper M, Yassin OM, Nusier M, Walker S. Localisation of a gene for prepubertal periodontitis to chromosome 11q14 and identification of a cathepsin C gene mutation. J Med Genet. 2000 Feb;37(2):95-101. PMID:10662808
↑ Hart PS, Zhang Y, Firatli E, Uygur C, Lotfazar M, Michalec MD, Marks JJ, Lu X, Coates BJ, Seow WK, Marshall R, Williams D, Reed JB, Wright JT, Hart TC. Identification of cathepsin C mutations in ethnically diverse papillon-Lefevre syndrome patients. J Med Genet. 2000 Dec;37(12):927-32. PMID:11106356
↑ Nakano A, Nomura K, Nakano H, Ono Y, LaForgia S, Pulkkinen L, Hashimoto I, Uitto J. Papillon-Lefevre syndrome: mutations and polymorphisms in the cathepsin C gene. J Invest Dermatol. 2001 Feb;116(2):339-43. PMID:11180012 doi:10.1046/j.1523-1747.2001.01244.x
↑ Lefevre C, Blanchet-Bardon C, Jobard F, Bouadjar B, Stalder JF, Cure S, Hoffmann A, Prud'Homme JF, Fischer J. Novel point mutations, deletions, and polymorphisms in the cathepsin C gene in nine families from Europe and North Africa with Papillon-Lefevre syndrome. J Invest Dermatol. 2001 Dec;117(6):1657-61. PMID:11886537 doi:1595
↑ Zhang Y, Lundgren T, Renvert S, Tatakis DN, Firatli E, Uygur C, Hart PS, Gorry MC, Marks JJ, Hart TC. Evidence of a founder effect for four cathepsin C gene mutations in Papillon-Lefevre syndrome patients. J Med Genet. 2001 Feb;38(2):96-101. PMID:11158173
↑ Zhang Y, Hart PS, Moretti AJ, Bouwsma OJ, Fisher EM, Dudlicek L, Pettenati MJ, Hart TC. Biochemical and mutational analyses of the cathepsin c gene (CTSC) in three North American families with Papillon Lefevre syndrome. Hum Mutat. 2002 Jul;20(1):75. PMID:12112662 doi:10.1002/humu.9040
↑ Hewitt C, McCormick D, Linden G, Turk D, Stern I, Wallace I, Southern L, Zhang L, Howard R, Bullon P, Wong M, Widmer R, Gaffar KA, Awawdeh L, Briggs J, Yaghmai R, Jabs EW, Hoeger P, Bleck O, Rudiger SG, Petersilka G, Battino M, Brett P, Hattab F, Al-Hamed M, Sloan P, Toomes C, Dixon M, James J, Read AP, Thakker N. The role of cathepsin C in Papillon-Lefevre syndrome, prepubertal periodontitis, and aggressive periodontitis. Hum Mutat. 2004 Mar;23(3):222-8. PMID:14974080 doi:10.1002/humu.10314
↑ de Haar SF, Jansen DC, Schoenmaker T, De Vree H, Everts V, Beertsen W. Loss-of-function mutations in cathepsin C in two families with Papillon-Lefevre syndrome are associated with deficiency of serine proteinases in PMNs. Hum Mutat. 2004 May;23(5):524. PMID:15108292 doi:10.1002/humu.9243
↑ de Haar SF, Mir M, Nguyen M, Kazemi B, Ramezani GH, Everts V, Beertsen W. Gene symbol: CTSC. Disease: Papillon-Lefevre syndrome. Hum Genet. 2005 May;116(6):545. PMID:15991336
↑ Hart TC, Hart PS, Michalec MD, Zhang Y, Firatli E, Van Dyke TE, Stabholz A, Zlotogorski A, Shapira L, Soskolne WA. Haim-Munk syndrome and Papillon-Lefevre syndrome are allelic mutations in cathepsin C. J Med Genet. 2000 Feb;37(2):88-94. PMID:10662807
↑ Hart TC, Hart PS, Michalec MD, Zhang Y, Marazita ML, Cooper M, Yassin OM, Nusier M, Walker S. Localisation of a gene for prepubertal periodontitis to chromosome 11q14 and identification of a cathepsin C gene mutation. J Med Genet. 2000 Feb;37(2):95-101. PMID:10662808
↑ Hewitt C, McCormick D, Linden G, Turk D, Stern I, Wallace I, Southern L, Zhang L, Howard R, Bullon P, Wong M, Widmer R, Gaffar KA, Awawdeh L, Briggs J, Yaghmai R, Jabs EW, Hoeger P, Bleck O, Rudiger SG, Petersilka G, Battino M, Brett P, Hattab F, Al-Hamed M, Sloan P, Toomes C, Dixon M, James J, Read AP, Thakker N. The role of cathepsin C in Papillon-Lefevre syndrome, prepubertal periodontitis, and aggressive periodontitis. Hum Mutat. 2004 Mar;23(3):222-8. PMID:14974080 doi:10.1002/humu.10314
↑ McGuire MJ, Lipsky PE, Thiele DL. Purification and characterization of dipeptidyl peptidase I from human spleen. Arch Biochem Biophys. 1992 Jun;295(2):280-8. PMID:1586157
↑ Molgaard A, Arnau J, Lauritzen C, Larsen S, Petersen G, Pedersen J. The crystal structure of human dipeptidyl peptidase I (cathepsin C) in complex with the inhibitor Gly-Phe-CHN2. Biochem J. 2007 Feb 1;401(3):645-50. PMID:17020538 doi:http://dx.doi.org/10.1042/BJ20061389

Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

OCA

[1] Allende LM, Garcia-Perez MA, Moreno A, Corell A, Carasol M, Martinez-Canut P, Arnaiz-Villena A. Cathepsin C gene: First compound heterozygous patient with Papillon-Lefevre syndrome and a novel symptomless mutation. Hum Mutat. 2001 Feb;17(2):152-3. PMID:11180601 doi:<152::AID-HUMU10>3.0.CO;2-# 10.1002/1098-1004(200102)17:2<152::AID-HUMU10>3.0.CO;2-#

[2] Allende LM, Moreno A, de Unamuno P. A genetic study of cathepsin C gene in two families with Papillon-Lefevre syndrome. Mol Genet Metab. 2003 Jun;79(2):146-8. PMID:12809647

[3] Toomes C, James J, Wood AJ, Wu CL, McCormick D, Lench N, Hewitt C, Moynihan L, Roberts E, Woods CG, Markham A, Wong M, Widmer R, Ghaffar KA, Pemberton M, Hussein IR, Temtamy SA, Davies R, Read AP, Sloan P, Dixon MJ, Thakker NS. Loss-of-function mutations in the cathepsin C gene result in periodontal disease and palmoplantar keratosis. Nat Genet. 1999 Dec;23(4):421-4. PMID:10581027 doi:10.1038/70525

[4] Hart TC, Hart PS, Michalec MD, Zhang Y, Marazita ML, Cooper M, Yassin OM, Nusier M, Walker S. Localisation of a gene for prepubertal periodontitis to chromosome 11q14 and identification of a cathepsin C gene mutation. J Med Genet. 2000 Feb;37(2):95-101. PMID:10662808

[5] Hart PS, Zhang Y, Firatli E, Uygur C, Lotfazar M, Michalec MD, Marks JJ, Lu X, Coates BJ, Seow WK, Marshall R, Williams D, Reed JB, Wright JT, Hart TC. Identification of cathepsin C mutations in ethnically diverse papillon-Lefevre syndrome patients. J Med Genet. 2000 Dec;37(12):927-32. PMID:11106356

[6] Nakano A, Nomura K, Nakano H, Ono Y, LaForgia S, Pulkkinen L, Hashimoto I, Uitto J. Papillon-Lefevre syndrome: mutations and polymorphisms in the cathepsin C gene. J Invest Dermatol. 2001 Feb;116(2):339-43. PMID:11180012 doi:10.1046/j.1523-1747.2001.01244.x

[7] Lefevre C, Blanchet-Bardon C, Jobard F, Bouadjar B, Stalder JF, Cure S, Hoffmann A, Prud'Homme JF, Fischer J. Novel point mutations, deletions, and polymorphisms in the cathepsin C gene in nine families from Europe and North Africa with Papillon-Lefevre syndrome. J Invest Dermatol. 2001 Dec;117(6):1657-61. PMID:11886537 doi:1595

[8] Zhang Y, Lundgren T, Renvert S, Tatakis DN, Firatli E, Uygur C, Hart PS, Gorry MC, Marks JJ, Hart TC. Evidence of a founder effect for four cathepsin C gene mutations in Papillon-Lefevre syndrome patients. J Med Genet. 2001 Feb;38(2):96-101. PMID:11158173

[9] Zhang Y, Hart PS, Moretti AJ, Bouwsma OJ, Fisher EM, Dudlicek L, Pettenati MJ, Hart TC. Biochemical and mutational analyses of the cathepsin c gene (CTSC) in three North American families with Papillon Lefevre syndrome. Hum Mutat. 2002 Jul;20(1):75. PMID:12112662 doi:10.1002/humu.9040

[10] Hewitt C, McCormick D, Linden G, Turk D, Stern I, Wallace I, Southern L, Zhang L, Howard R, Bullon P, Wong M, Widmer R, Gaffar KA, Awawdeh L, Briggs J, Yaghmai R, Jabs EW, Hoeger P, Bleck O, Rudiger SG, Petersilka G, Battino M, Brett P, Hattab F, Al-Hamed M, Sloan P, Toomes C, Dixon M, James J, Read AP, Thakker N. The role of cathepsin C in Papillon-Lefevre syndrome, prepubertal periodontitis, and aggressive periodontitis. Hum Mutat. 2004 Mar;23(3):222-8. PMID:14974080 doi:10.1002/humu.10314

[11] Haar SF, Jansen DC, Schoenmaker T, De Vree H, Everts V, Beertsen W. Loss-of-function mutations in cathepsin C in two families with Papillon-Lefevre syndrome are associated with deficiency of serine proteinases in PMNs. Hum Mutat. 2004 May;23(5):524. PMID:15108292 doi:10.1002/humu.9243

[12] Haar SF, Mir M, Nguyen M, Kazemi B, Ramezani GH, Everts V, Beertsen W. Gene symbol: CTSC. Disease: Papillon-Lefevre syndrome. Hum Genet. 2005 May;116(6):545. PMID:15991336

[13] Hart TC, Hart PS, Michalec MD, Zhang Y, Firatli E, Van Dyke TE, Stabholz A, Zlotogorski A, Shapira L, Soskolne WA. Haim-Munk syndrome and Papillon-Lefevre syndrome are allelic mutations in cathepsin C. J Med Genet. 2000 Feb;37(2):88-94. PMID:10662807

[14] Hart TC, Hart PS, Michalec MD, Zhang Y, Marazita ML, Cooper M, Yassin OM, Nusier M, Walker S. Localisation of a gene for prepubertal periodontitis to chromosome 11q14 and identification of a cathepsin C gene mutation. J Med Genet. 2000 Feb;37(2):95-101. PMID:10662808

[15] Hewitt C, McCormick D, Linden G, Turk D, Stern I, Wallace I, Southern L, Zhang L, Howard R, Bullon P, Wong M, Widmer R, Gaffar KA, Awawdeh L, Briggs J, Yaghmai R, Jabs EW, Hoeger P, Bleck O, Rudiger SG, Petersilka G, Battino M, Brett P, Hattab F, Al-Hamed M, Sloan P, Toomes C, Dixon M, James J, Read AP, Thakker N. The role of cathepsin C in Papillon-Lefevre syndrome, prepubertal periodontitis, and aggressive periodontitis. Hum Mutat. 2004 Mar;23(3):222-8. PMID:14974080 doi:10.1002/humu.10314

[16] McGuire MJ, Lipsky PE, Thiele DL. Purification and characterization of dipeptidyl peptidase I from human spleen. Arch Biochem Biophys. 1992 Jun;295(2):280-8. PMID:1586157

[17] Molgaard A, Arnau J, Lauritzen C, Larsen S, Petersen G, Pedersen J. The crystal structure of human dipeptidyl peptidase I (cathepsin C) in complex with the inhibitor Gly-Phe-CHN2. Biochem J. 2007 Feb 1;401(3):645-50. PMID:17020538 doi:http://dx.doi.org/10.1042/BJ20061389

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@@ Line 2: / Line 2: @@
 <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/Homo_sapiens Homo sapiens]. 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>
+<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 Homo sapiens])</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://www.rcsb.org/pdb/explore.do?structureId=2djg RCSB], [http://www.ebi.ac.uk/pdbsum/2djg PDBsum]</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]</span></td></tr>
 </table>
 == Disease ==
@@ Line 31: / Line 31: @@
 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==
@@ Line 40: / Line 41: @@
 </StructureSection>
 [[Category: Dipeptidyl-peptidase I]]
-[[Category: Homo sapiens]]
+[[Category: Human]]
 [[Category: Arnau, J]]
 [[Category: Larsen, S]]

2djg: Difference between revisions

Revision as of 09:54, 11 September 2015

Re-determination of the native structure of human dipeptidyl peptidase I (cathepsin C)Re-determination of the native structure of human dipeptidyl peptidase I (cathepsin C)

Structural highlights

Disease

Function

Evolutionary Conservation

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

Navigation menu

2djg: Difference between revisions

Revision as of 09:54, 11 September 2015

Re-determination of the native structure of human dipeptidyl peptidase I (cathepsin C)Re-determination of the native structure of human dipeptidyl peptidase I (cathepsin C)

Structural highlights

Disease

Function

Evolutionary Conservation

Publication Abstract from PubMed

See Also

References

Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

Navigation menu

Search