3ee6

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{{STRUCTURE_3ee6| PDB=3ee6 | SCENE= }}
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==Crystal Structure Analysis of Tripeptidyl peptidase -I==
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===Crystal Structure Analysis of Tripeptidyl peptidase -I===
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<StructureSection load='3ee6' size='340' side='right' caption='[[3ee6]], [[Resolution|resolution]] 2.35&Aring;' scene=''>
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{{ABSTRACT_PUBMED_19038966}}
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== Structural highlights ==
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<table><tr><td colspan='2'>[[3ee6]] is a 2 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=3EE6 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3EE6 FirstGlance]. <br>
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</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=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
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<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">CLN2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</td></tr>
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<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>
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<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=3ee6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3ee6 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3ee6 RCSB], [http://www.ebi.ac.uk/pdbsum/3ee6 PDBsum]</span></td></tr>
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</table>
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== Disease ==
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[[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>
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== Function ==
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[[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).
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== Evolutionary Conservation ==
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[[Image:Consurf_key_small.gif|200px|right]]
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Check<jmol>
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<jmolCheckbox>
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<scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/ee/3ee6_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
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<text>to colour the structure by Evolutionary Conservation</text>
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</jmolCheckbox>
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</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].
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<div style="clear:both"></div>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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Late infantile neuronal ceroid lipofuscinosis, a fatal neurodegenerative disease of childhood, is caused by mutations in the TPP1 gene that encodes tripeptidyl-peptidase I. We show that purified TPP1 requires at least partial glycosylation for in vitro autoprocessing and proteolytic activity. We crystallized the fully glycosylated TPP1 precursor under conditions that implied partial autocatalytic cleavage between the prosegment and the catalytic domain. X-ray crystallographic analysis at 2.35 angstroms resolution reveals a globular structure with a subtilisin-like fold, a Ser475-Glu272-Asp360 catalytic triad, and an octahedrally coordinated Ca2+-binding site that are characteristic features of the S53 sedolisin family of peptidases. In contrast to other S53 peptidases, the TPP1 structure revealed steric constraints on the P4 substrate pocket explaining its preferential cleavage of tripeptides from the unsubstituted N terminus of proteins. Two alternative conformations of the catalytic Asp276 are associated with the activation status of TPP1. 28 disease-causing missense mutations are analyzed in the light of the TPP1 structure providing insight into the molecular basis of late infantile neuronal ceroid lipofuscinosis.
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==Disease==
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Structure of tripeptidyl-peptidase I provides insight into the molecular basis of late infantile neuronal ceroid lipofuscinosis.,Pal A, Kraetzner R, Gruene T, Grapp M, Schreiber K, Gronborg M, Urlaub H, Becker S, Asif AR, Gartner J, Sheldrick GM, Steinfeld R J Biol Chem. 2009 Feb 6;284(6):3976-84. Epub 2008 Nov 26. PMID:19038966<ref>PMID:19038966</ref>
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[[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>
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==Function==
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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[[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).
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</div>
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==About this Structure==
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[[3ee6]] is a 2 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=3EE6 OCA].
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==See Also==
==See Also==
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*[[Aminopeptidase|Aminopeptidase]]
*[[Tripeptidyl peptidase|Tripeptidyl peptidase]]
*[[Tripeptidyl peptidase|Tripeptidyl peptidase]]
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== References ==
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==Reference==
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<references/>
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<ref group="xtra">PMID:019038966</ref><references group="xtra"/><references/>
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__TOC__
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: Tripeptidyl-peptidase I]]
[[Category: Tripeptidyl-peptidase I]]
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[[Category: Asif, A R.]]
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[[Category: Asif, A R]]
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[[Category: Becker, S.]]
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[[Category: Becker, S]]
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[[Category: Gartner, J.]]
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[[Category: Gartner, J]]
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[[Category: Granborg, M.]]
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[[Category: Granborg, M]]
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[[Category: Grapp, M.]]
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[[Category: Grapp, M]]
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[[Category: Gruene, T.]]
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[[Category: Gruene, T]]
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[[Category: Kraetzner, R.]]
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[[Category: Kraetzner, R]]
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[[Category: Pal, A.]]
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[[Category: Pal, A]]
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[[Category: Schreiber, K.]]
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[[Category: Schreiber, K]]
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[[Category: Sheldrick, G M.]]
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[[Category: Sheldrick, G M]]
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[[Category: Steinfeld, R.]]
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[[Category: Steinfeld, R]]
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[[Category: Urlaub, H.]]
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[[Category: Urlaub, H]]
[[Category: Disease mutation]]
[[Category: Disease mutation]]
[[Category: Epilepsy]]
[[Category: Epilepsy]]

Revision as of 13:21, 18 December 2014

Crystal Structure Analysis of Tripeptidyl peptidase -I

3ee6, resolution 2.35Å

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