1lyb

From Proteopedia

(Difference between revisions)
Jump to: navigation, search
Current revision (07:30, 23 October 2024) (edit) (undo)
 
(20 intermediate revisions not shown.)
Line 1: Line 1:
-
[[Image:1lyb.jpg|left|200px]]
 
-
{{Structure
+
==CRYSTAL STRUCTURES OF NATIVE AND INHIBITED FORMS OF HUMAN CATHEPSIN D: IMPLICATIONS FOR LYSOSOMAL TARGETING AND DRUG DESIGN==
-
|PDB= 1lyb |SIZE=350|CAPTION= <scene name='initialview01'>1lyb</scene>, resolution 2.5&Aring;
+
<StructureSection load='1lyb' size='340' side='right'caption='[[1lyb]], [[Resolution|resolution]] 2.50&Aring;' scene=''>
-
|SITE=
+
== Structural highlights ==
-
|LIGAND= <scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=IVA:ISOVALERIC+ACID'>IVA</scene>, <scene name='pdbligand=MAN:ALPHA-D-MANNOSE'>MAN</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=STA:STATINE'>STA</scene>
+
<table><tr><td colspan='2'>[[1lyb]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Streptomyces_argenteolus_subsp._toyonakensis Streptomyces argenteolus subsp. toyonakensis]. The December 2000 RCSB PDB [https://pdb.rcsb.org/pdb/static.do?p=education_discussion/molecule_of_the_month/index.html Molecule of the Month] feature on ''Pepsin'' by David S. Goodsell is [https://dx.doi.org/10.2210/rcsb_pdb/mom_2000_12 10.2210/rcsb_pdb/mom_2000_12]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1LYB OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1LYB FirstGlance]. <br>
-
|ACTIVITY= <span class='plainlinks'>[http://en.wikipedia.org/wiki/Cathepsin_D Cathepsin D], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.23.5 3.4.23.5] </span>
+
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.5&#8491;</td></tr>
-
|GENE=
+
<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=IVA:ISOVALERIC+ACID'>IVA</scene>, <scene name='pdbligand=MAN:ALPHA-D-MANNOSE'>MAN</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=STA:STATINE'>STA</scene></td></tr>
-
|DOMAIN=
+
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1lyb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1lyb OCA], [https://pdbe.org/1lyb PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1lyb RCSB], [https://www.ebi.ac.uk/pdbsum/1lyb PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1lyb ProSAT]</span></td></tr>
-
|RELATEDENTRY=
+
</table>
-
|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1lyb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1lyb OCA], [http://www.ebi.ac.uk/pdbsum/1lyb PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1lyb RCSB]</span>
+
== Disease ==
-
}}
+
[https://www.uniprot.org/uniprot/CATD_HUMAN CATD_HUMAN] Defects in CTSD are the cause of neuronal ceroid lipofuscinosis type 10 (CLN10) [MIM:[https://omim.org/entry/610127 610127]; also known as neuronal ceroid lipofuscinosis due to cathepsin D deficiency. A form of neuronal ceroid lipofuscinosis with onset at birth or early childhood. 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.<ref>PMID:16670177</ref> <ref>PMID:16685649</ref> <ref>PMID:21990111</ref>
 +
== Function ==
 +
[https://www.uniprot.org/uniprot/CATD_HUMAN CATD_HUMAN] Acid protease active in intracellular protein breakdown. Involved in the pathogenesis of several diseases such as breast cancer and possibly Alzheimer disease.
 +
== 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/ly/1lyb_consurf.spt"</scriptWhenChecked>
 +
<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.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/main_output.php?pdb_ID=1lyb ConSurf].
 +
<div style="clear:both"></div>
 +
<div style="background-color:#fffaf0;">
 +
== Publication Abstract from PubMed ==
 +
Cathepsin D (EC 3.4.23.5) is a lysosomal protease suspected to play important roles in protein catabolism, antigen processing, degenerative diseases, and breast cancer progression. Determination of the crystal structures of cathepsin D and a complex with pepstatin at 2.5 A resolution provides insights into inhibitor binding and lysosomal targeting for this two-chain, N-glycosylated aspartic protease. Comparison with the structures of a complex of pepstatin bound to rhizopuspepsin and with a human renin-inhibitor complex revealed differences in subsite structures and inhibitor-enzyme interactions that are consistent with affinity differences and structure-activity relationships and suggest strategies for fine-tuning the specificity of cathepsin D inhibitors. Mutagenesis studies have identified a phosphotransferase recognition region that is required for oligosaccharide phosphorylation but is 32 A distant from the N-domain glycosylation site at Asn-70. Electron density for the crystal structure of cathepsin D indicated the presence of an N-linked oligosaccharide that extends from Asn-70 toward Lys-203, which is a key component of the phosphotransferase recognition region, and thus provides a structural explanation for how the phosphotransferase can recognize apparently distant sites on the protein surface.
-
'''CRYSTAL STRUCTURES OF NATIVE AND INHIBITED FORMS OF HUMAN CATHEPSIN D: IMPLICATIONS FOR LYSOSOMAL TARGETING AND DRUG DESIGN'''
+
Crystal structures of native and inhibited forms of human cathepsin D: implications for lysosomal targeting and drug design.,Baldwin ET, Bhat TN, Gulnik S, Hosur MV, Sowder RC 2nd, Cachau RE, Collins J, Silva AM, Erickson JW Proc Natl Acad Sci U S A. 1993 Jul 15;90(14):6796-800. PMID:8393577<ref>PMID:8393577</ref>
 +
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 +
</div>
 +
<div class="pdbe-citations 1lyb" style="background-color:#fffaf0;"></div>
-
==Overview==
+
==See Also==
-
Cathepsin D (EC 3.4.23.5) is a lysosomal protease suspected to play important roles in protein catabolism, antigen processing, degenerative diseases, and breast cancer progression. Determination of the crystal structures of cathepsin D and a complex with pepstatin at 2.5 A resolution provides insights into inhibitor binding and lysosomal targeting for this two-chain, N-glycosylated aspartic protease. Comparison with the structures of a complex of pepstatin bound to rhizopuspepsin and with a human renin-inhibitor complex revealed differences in subsite structures and inhibitor-enzyme interactions that are consistent with affinity differences and structure-activity relationships and suggest strategies for fine-tuning the specificity of cathepsin D inhibitors. Mutagenesis studies have identified a phosphotransferase recognition region that is required for oligosaccharide phosphorylation but is 32 A distant from the N-domain glycosylation site at Asn-70. Electron density for the crystal structure of cathepsin D indicated the presence of an N-linked oligosaccharide that extends from Asn-70 toward Lys-203, which is a key component of the phosphotransferase recognition region, and thus provides a structural explanation for how the phosphotransferase can recognize apparently distant sites on the protein surface.
+
*[[Cathepsin 3D structures|Cathepsin 3D structures]]
-
 
+
== References ==
-
==About this Structure==
+
<references/>
-
1LYB is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. The following page contains interesting information on the relation of 1LYB with [[http://pdb.rcsb.org/pdb/static.do?p=education_discussion/molecule_of_the_month/pdb12_1.html Pepsin]]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1LYB OCA].
+
__TOC__
-
 
+
</StructureSection>
-
==Reference==
+
-
Crystal structures of native and inhibited forms of human cathepsin D: implications for lysosomal targeting and drug design., Baldwin ET, Bhat TN, Gulnik S, Hosur MV, Sowder RC 2nd, Cachau RE, Collins J, Silva AM, Erickson JW, Proc Natl Acad Sci U S A. 1993 Jul 15;90(14):6796-800. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/8393577 8393577]
+
-
[[Category: Cathepsin D]]
+
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
 +
[[Category: Large Structures]]
[[Category: Pepsin]]
[[Category: Pepsin]]
-
[[Category: Single protein]]
+
[[Category: RCSB PDB Molecule of the Month]]
-
[[Category: Baldwin, E T.]]
+
[[Category: Streptomyces argenteolus subsp. toyonakensis]]
-
[[Category: Bhat, T N.]]
+
[[Category: Baldwin ET]]
-
[[Category: Erickson, J W.]]
+
[[Category: Bhat TN]]
-
[[Category: Gulnik, S.]]
+
[[Category: Erickson JW]]
-
[[Category: lysosomal aspartic protease]]
+
[[Category: Gulnik S]]
-
 
+
-
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Mar 30 22:08:52 2008''
+

Current revision

CRYSTAL STRUCTURES OF NATIVE AND INHIBITED FORMS OF HUMAN CATHEPSIN D: IMPLICATIONS FOR LYSOSOMAL TARGETING AND DRUG DESIGN

PDB ID 1lyb

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/1lyb"
Personal tools