3edy

From Proteopedia

(Difference between revisions)
Jump to: navigation, search
Line 1: Line 1:
-
{{STRUCTURE_3edy| PDB=3edy | SCENE= }}
+
==Crystal Structure of the Precursor Form of Human Tripeptidyl-Peptidase 1==
-
===Crystal Structure of the Precursor Form of Human Tripeptidyl-Peptidase 1===
+
<StructureSection load='3edy' size='340' side='right' caption='[[3edy]], [[Resolution|resolution]] 1.85&Aring;' scene=''>
-
{{ABSTRACT_PUBMED_19038967}}
+
== Structural highlights ==
 +
<table><tr><td colspan='2'>[[3edy]] is a 1 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=3EDY OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3EDY FirstGlance]. <br>
 +
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></td></tr>
 +
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">TPP1, CLN2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</td></tr>
 +
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Tripeptidyl-peptidase_I Tripeptidyl-peptidase I], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.14.9 3.4.14.9] </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=3edy FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3edy OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3edy RCSB], [http://www.ebi.ac.uk/pdbsum/3edy PDBsum]</span></td></tr>
 +
</table>
 +
== Disease ==
 +
[[http://www.uniprot.org/uniprot/TPP1_HUMAN TPP1_HUMAN]] Defects in TPP1 are the cause of neuronal ceroid lipofuscinosis type 2 (CLN2) [MIM:[http://omim.org/entry/204500 204500]]. A form of neuronal ceroid lipofuscinosis. Neuronal ceroid lipofuscinoses are progressive neurodegenerative, lysosomal storage diseases characterized by intracellular accumulation of autofluorescent liposomal material, and clinically by seizures, dementia, visual loss, and/or cerebral atrophy. The lipopigment pattern seen most often in CLN2 consists of curvilinear profiles.<ref>PMID:9295267</ref> <ref>PMID:10330339</ref> <ref>PMID:10665500</ref> <ref>PMID:11339651</ref> <ref>PMID:11241479</ref> <ref>PMID:11589012</ref> <ref>PMID:12376936</ref> <ref>PMID:12414822</ref> <ref>PMID:12698559</ref> <ref>PMID:14736728</ref> <ref>PMID:19201763</ref> <ref>PMID:20340139</ref> <ref>PMID:21990111</ref>
 +
== Function ==
 +
[[http://www.uniprot.org/uniprot/TPP1_HUMAN TPP1_HUMAN]] Lysosomal serine protease with tripeptidyl-peptidase I activity. May act as a non-specific lysosomal peptidase which generates tripeptides from the breakdown products produced by lysosomal proteinases. Requires substrates with an unsubstituted N-terminus (By similarity).
 +
== 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/ed/3edy_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/chain_selection.php?pdb_ID=2ata ConSurf].
 +
<div style="clear:both"></div>
 +
<div style="background-color:#fffaf0;">
 +
== Publication Abstract from PubMed ==
 +
Late infantile neuronal ceroid lipofuscinosis is a fatal childhood neurological disorder caused by a deficiency in the lysosomal protease tripeptidyl-peptidase 1 (TPP1). TPP1 represents the only known mammalian member of the S53 family of serine proteases, a group characterized by a subtilisin-like fold, a Ser-Glu-Asp catalytic triad, and an acidic pH optimum. TPP1 is synthesized as an inactive proenzyme (pro-TPP1) that is proteolytically processed into the active enzyme after exposure to low pH in vitro or targeting to the lysosome in vivo. In this study, we describe an endoglycosidase H-deglycosylated form of TPP1 containing four Asn-linked N-acetylglucosamines that is indistinguishable from fully glycosylated TPP1 in terms of autocatalytic processing of the proform and enzymatic properties of the mature protease. The crystal structure of deglycosylated pro-TPP1 was determined at 1.85 A resolution. A large 151-residue C-shaped prodomain makes extensive contacts as it wraps around the surface of the catalytic domain with the two domains connected by a 24-residue flexible linker that passes through the substrate-binding groove. The proenzyme structure reveals suboptimal catalytic triad geometry with its propiece linker partially blocking the substrate-binding site, which together serve to prevent premature activation of the protease. Finally, we have identified numerous processing intermediates and propose a structural model that explains the pathway for TPP1 activation in vitro. These data provide new insights into TPP1 function and represent a valuable resource for constructing improved TPP1 variants for treatment of late infantile neuronal ceroid lipofuscinosis.
-
==Disease==
+
Crystal Structure and Autoactivation Pathway of the Precursor Form of Human Tripeptidyl-peptidase 1, the Enzyme Deficient in Late Infantile Ceroid Lipofuscinosis.,Guhaniyogi J, Sohar I, Das K, Stock AM, Lobel P J Biol Chem. 2009 Feb 6;284(6):3985-97. Epub 2008 Nov 26. PMID:19038967<ref>PMID:19038967</ref>
-
[[http://www.uniprot.org/uniprot/TPP1_HUMAN TPP1_HUMAN]] Defects in TPP1 are the cause of neuronal ceroid lipofuscinosis type 2 (CLN2) [MIM:[http://omim.org/entry/204500 204500]]. A form of neuronal ceroid lipofuscinosis. Neuronal ceroid lipofuscinoses are progressive neurodegenerative, lysosomal storage diseases characterized by intracellular accumulation of autofluorescent liposomal material, and clinically by seizures, dementia, visual loss, and/or cerebral atrophy. The lipopigment pattern seen most often in CLN2 consists of curvilinear profiles.<ref>PMID:9295267</ref><ref>PMID:10330339</ref><ref>PMID:10665500</ref><ref>PMID:11339651</ref><ref>PMID:11241479</ref><ref>PMID:11589012</ref><ref>PMID:12376936</ref><ref>PMID:12414822</ref><ref>PMID:12698559</ref><ref>PMID:14736728</ref><ref>PMID:19201763</ref><ref>PMID:20340139</ref><ref>PMID:21990111</ref>
+
-
==Function==
+
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-
[[http://www.uniprot.org/uniprot/TPP1_HUMAN TPP1_HUMAN]] Lysosomal serine protease with tripeptidyl-peptidase I activity. May act as a non-specific lysosomal peptidase which generates tripeptides from the breakdown products produced by lysosomal proteinases. Requires substrates with an unsubstituted N-terminus (By similarity).
+
</div>
-
 
+
-
==About this Structure==
+
-
[[3edy]] is a 1 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=3EDY OCA].
+
==See Also==
==See Also==
 +
*[[Aminopeptidase|Aminopeptidase]]
*[[Tripeptidyl peptidase|Tripeptidyl peptidase]]
*[[Tripeptidyl peptidase|Tripeptidyl peptidase]]
-
 
+
== References ==
-
==Reference==
+
<references/>
-
<ref group="xtra">PMID:019038967</ref><references group="xtra"/><references/>
+
__TOC__
 +
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: Tripeptidyl-peptidase I]]
[[Category: Tripeptidyl-peptidase I]]
-
[[Category: Das, K.]]
+
[[Category: Das, K]]
-
[[Category: Guhaniyogi, J.]]
+
[[Category: Guhaniyogi, J]]
-
[[Category: Lobel, P.]]
+
[[Category: Lobel, P]]
-
[[Category: Sohar, I.]]
+
[[Category: Sohar, I]]
-
[[Category: Stock, A M.]]
+
[[Category: Stock, A M]]
[[Category: Batten disease]]
[[Category: Batten disease]]
[[Category: Catalytic triad]]
[[Category: Catalytic triad]]

Revision as of 13:09, 18 December 2014

Crystal Structure of the Precursor Form of Human Tripeptidyl-Peptidase 1

3edy, resolution 1.85Å

Drag the structure with the mouse to rotate

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/3edy"
Personal tools