4mws: Difference between revisions
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==Crystal structure of human PPCA (trigonal crystal form 1)== | ==Crystal structure of human PPCA (trigonal crystal form 1)== | ||
<StructureSection load='4mws' size='340' side='right' caption='[[4mws]], [[Resolution|resolution]] 2.80Å' scene=''> | <StructureSection load='4mws' size='340' side='right' caption='[[4mws]], [[Resolution|resolution]] 2.80Å' scene=''> | ||
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<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">CTSA, PPGB ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr> | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">CTSA, PPGB ([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/Carboxypeptidase_C Carboxypeptidase C], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.16.5 3.4.16.5] </span></td></tr> | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Carboxypeptidase_C Carboxypeptidase C], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.16.5 3.4.16.5] </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=4mws FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4mws OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4mws RCSB], [http://www.ebi.ac.uk/pdbsum/4mws 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=4mws FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4mws OCA], [http://pdbe.org/4mws PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4mws RCSB], [http://www.ebi.ac.uk/pdbsum/4mws PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4mws ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Disease == | == Disease == | ||
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
</div> | </div> | ||
<div class="pdbe-citations 4mws" style="background-color:#fffaf0;"></div> | |||
==See Also== | ==See Also== | ||
Revision as of 20:23, 18 January 2017
Crystal structure of human PPCA (trigonal crystal form 1)Crystal structure of human PPCA (trigonal crystal form 1)
Structural highlights
Disease[PPGB_HUMAN] Defects in CTSA are the cause of galactosialidosis (GSL) [MIM:256540]. A lysosomal storage disease associated with a combined deficiency of beta-galactosidase and neuraminidase, secondary to a defect in cathepsin A. All patients have clinical manifestations typical of a lysosomal disorder, such as coarse facies, cherry red spots, vertebral changes, foam cells in the bone marrow, and vacuolated lymphocytes. Three phenotypic subtypes are recognized. The early infantile form is associated with fetal hydrops, edema, ascites, visceromegaly, skeletal dysplasia, and early death. The late infantile type is characterized by hepatosplenomegaly, growth retardation, cardiac involvement, and a normal or mildly affected mental state. The juvenile/adult form is characterized by myoclonus, ataxia, angiokeratoma, mental retardation, neurologic deterioration, absence of visceromegaly, and long survival.[1] [2] [3] [4] Function[PPGB_HUMAN] Protective protein appears to be essential for both the activity of beta-galactosidase and neuraminidase, it associates with these enzymes and exerts a protective function necessary for their stability and activity. This protein is also a carboxypeptidase and can deamidate tachykinins.[5] Publication Abstract from PubMedGalactosialidosis is a human lysosomal storage disease caused by deficiency in the multifunctional lysosomal protease cathepsin A (also known as protective protein/cathepsin A, PPCA, catA, HPP, and CTSA; EC 3.4.16.5). Previous structural work on the inactive precursor human cathepsin A (zymogen) led to a two-stage model for activation, where proteolysis of a 1.6-kDa excision peptide is followed by a conformational change in a blocking peptide occluding the active site. Here we present evidence for an alternate model of activation of human cathepsin A, needing only cleavage of a 3.3-kDa excision peptide to yield full enzymatic activity, with no conformational change required. We present x-ray crystallographic, mass spectrometric, amino acid sequencing, enzymatic, and cellular data to support the cleavage-only activation model. The results clarify a longstanding question about the mechanism of cathepsin A activation and point to new avenues for the design of mechanism-based inhibitors of the enzyme. Proteolytic activation of human cathepsin A.,Kolli N, Garman SC J Biol Chem. 2014 Apr 25;289(17):11592-600. doi: 10.1074/jbc.M113.524280. Epub, 2014 Mar 5. PMID:24599961[6] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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