6qcb

From Proteopedia

(Difference between revisions)
Jump to: navigation, search
Current revision (11:57, 24 January 2024) (edit) (undo)
 
(One intermediate revision not shown.)
Line 3: Line 3:
<StructureSection load='6qcb' size='340' side='right'caption='[[6qcb]], [[Resolution|resolution]] 1.55&Aring;' scene=''>
<StructureSection load='6qcb' size='340' side='right'caption='[[6qcb]], [[Resolution|resolution]] 1.55&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
-
<table><tr><td colspan='2'>[[6qcb]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6QCB OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6QCB FirstGlance]. <br>
+
<table><tr><td colspan='2'>[[6qcb]] 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=6QCB OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6QCB FirstGlance]. <br>
-
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=DMS:DIMETHYL+SULFOXIDE'>DMS</scene>, <scene name='pdbligand=HWE:(3~{S},7~{S},8~{S})-7-oxidanyl-8-(phenylmethyl)-3-propan-2-yl-1,4,9-triazacyclohenicosane-2,5,10-trione'>HWE</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=PO3:PHOSPHITE+ION'>PO3</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
+
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.55&#8491;</td></tr>
-
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><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='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=DMS:DIMETHYL+SULFOXIDE'>DMS</scene>, <scene name='pdbligand=HWE:(3~{S},7~{S},8~{S})-7-oxidanyl-8-(phenylmethyl)-3-propan-2-yl-1,4,9-triazacyclohenicosane-2,5,10-trione'>HWE</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=PO3:PHOSPHITE+ION'>PO3</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></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=6qcb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6qcb OCA], [http://pdbe.org/6qcb PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6qcb RCSB], [http://www.ebi.ac.uk/pdbsum/6qcb PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6qcb ProSAT]</span></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=6qcb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6qcb OCA], [https://pdbe.org/6qcb PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6qcb RCSB], [https://www.ebi.ac.uk/pdbsum/6qcb PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6qcb ProSAT]</span></td></tr>
</table>
</table>
== Disease ==
== Disease ==
-
[[http://www.uniprot.org/uniprot/CATD_HUMAN CATD_HUMAN]] Defects in CTSD are the cause of neuronal ceroid lipofuscinosis type 10 (CLN10) [MIM:[http://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>
+
[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 ==
== Function ==
-
[[http://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.
+
[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.
 +
<div style="background-color:#fffaf0;">
 +
== Publication Abstract from PubMed ==
 +
Human cathepsin D (CatD), a pepsin-family aspartic protease, plays an important role in tumor progression and metastasis. Here, we report the development of biomimetic inhibitors of CatD as novel tools for regulation of this therapeutic target. We designed a macrocyclic scaffold to mimic the spatial conformation of the minimal pseudo-dipeptide binding motif of pepstatin A, a microbial oligopeptide inhibitor, in the CatD active site. A library of more than 30 macrocyclic peptidomimetic inhibitors was employed for scaffold optimization, mapping of subsite interactions, and profiling of inhibitor selectivity. Furthermore, we solved high-resolution crystal structures of three macrocyclic inhibitors with low nanomolar or subnanomolar potency in complex with CatD and determined their binding mode using quantum chemical calculations. The study provides a new structural template and functional profile that can be exploited for design of potential chemotherapeutics that specifically inhibit CatD and related aspartic proteases.
 +
 
 +
Biomimetic Macrocyclic Inhibitors of Human Cathepsin D: Structure-Activity Relationship and Binding Mode Analysis.,Houstecka R, Hadzima M, Fanfrlik J, Brynda J, Pallova L, Hanova I, Mertlikova-Kaiserova H, Lepsik M, Horn M, Smrcina M, Majer P, Mares M J Med Chem. 2020 Feb 13. doi: 10.1021/acs.jmedchem.9b01351. PMID:32003991<ref>PMID:32003991</ref>
 +
 
 +
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 +
</div>
 +
<div class="pdbe-citations 6qcb" style="background-color:#fffaf0;"></div>
 +
 
 +
==See Also==
 +
*[[Cathepsin 3D structures|Cathepsin 3D structures]]
== References ==
== References ==
<references/>
<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
-
[[Category: Cathepsin D]]
+
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Large Structures]]
-
[[Category: Brynda, J]]
+
[[Category: Brynda J]]
-
[[Category: Houstecka, R]]
+
[[Category: Houstecka R]]
-
[[Category: Majer, P]]
+
[[Category: Majer P]]
-
[[Category: Mares, M]]
+
[[Category: Mares M]]
-
[[Category: Aspartic protease]]
+
-
[[Category: Hydrolase]]
+
-
[[Category: Peptidomimetic inhibitor]]
+

Current revision

Crystal structure of human cathepsin D in complex with macrocyclic inhibitor 9

PDB ID 6qcb

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/6qcb"
Personal tools