4mwt: Difference between revisions

← Older edit

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

OCA

@@ Line 1: / Line 1: @@
-{{STRUCTURE_4mwt|  PDB=4mwt  |  SCENE=  }}
-===Crystal structure of human PPCA (trigonal crystal form 2)===
-==Disease==
+==Crystal structure of human PPCA (trigonal crystal form 2)==
-[[http://www.uniprot.org/uniprot/PPGB_HUMAN PPGB_HUMAN]] Defects in CTSA are the cause of galactosialidosis (GSL) [MIM:[http://omim.org/entry/256540 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.<ref>PMID:1756715</ref> <ref>PMID:8514852</ref> <ref>PMID:8968752</ref> <ref>PMID:10944848</ref>
+<StructureSection load='4mwt' size='340' side='right'caption='[[4mwt]], [[Resolution|resolution]] 3.85&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[4mwt]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4MWT OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4MWT FirstGlance]. <br>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 3.85&#8491;</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4mwt FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4mwt OCA], [https://pdbe.org/4mwt PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4mwt RCSB], [https://www.ebi.ac.uk/pdbsum/4mwt PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4mwt ProSAT]</span></td></tr>
+</table>
+== Disease ==
+[https://www.uniprot.org/uniprot/PPGB_HUMAN PPGB_HUMAN] Defects in CTSA are the cause of galactosialidosis (GSL) [MIM:[https://omim.org/entry/256540 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.<ref>PMID:1756715</ref> <ref>PMID:8514852</ref> <ref>PMID:8968752</ref> <ref>PMID:10944848</ref>
+== Function ==
+[https://www.uniprot.org/uniprot/PPGB_HUMAN 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.<ref>PMID:1907282</ref>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+Galactosialidosis 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.
-==Function==
+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<ref>PMID:24599961</ref>
-[[http://www.uniprot.org/uniprot/PPGB_HUMAN 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.<ref>PMID:1907282</ref>
-==About this Structure==
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-[[4mwt]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4MWT OCA].
+</div>
+<div class="pdbe-citations 4mwt" style="background-color:#fffaf0;"></div>
-==Reference==
+==See Also==
-<references group="xtra"/><references/>
+*[[Cathepsin 3D structures|Cathepsin 3D structures]]
-[[Category: Carboxypeptidase C]]
+== References ==
-[[Category: Garman, S C.]]
+<references/>
-[[Category: Kolli, N.]]
+__TOC__
-[[Category: Carboxypeptidase]]
+</StructureSection>
-[[Category: Cathepsin some]]
+[[Category: Homo sapiens]]
-[[Category: Glycoprotein]]
+[[Category: Large Structures]]
-[[Category: Hydrolase]]
+[[Category: Garman SC]]
-[[Category: Lysosomal enzyme]]
+[[Category: Kolli N]]
-[[Category: N-linked glycosylation]]
-[[Category: Protective protein]]
-[[Category: Proteolytically activated form]]
-[[Category: Serine protease]]