View source for 6jd8


==Structure of a proline specific mutant of human cathepsin L==
<StructureSection load='6jd8' size='340' side='right'caption='[[6jd8]], [[Resolution|resolution]] 1.46&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6jd8]] is a 1 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=6JD8 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6JD8 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]] 1.457&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=EOH:ETHANOL'>EOH</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</scene>, <scene name='pdbligand=PGE:TRIETHYLENE+GLYCOL'>PGE</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=6jd8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6jd8 OCA], [https://pdbe.org/6jd8 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6jd8 RCSB], [https://www.ebi.ac.uk/pdbsum/6jd8 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6jd8 ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/CATL1_HUMAN CATL1_HUMAN] Important for the overall degradation of proteins in lysosomes.
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Engineering precise substrate specificity of proteases advances the potential to use them in biotechnological and therapeutic applications. Collagen degradation, a physiological process mediated by collagenases, is an integral part of extracellular matrix remodeling and when uncontrolled, implicated in different pathological conditions. Lysosomal cathepsin-K cleaves triple helical collagen fiber, whereas cathepsin-L cannot do so. In this study, we have imparted collagenolytic property to cathepsin-L, by systematically engineering proline-specificity and glycosaminoglycans (GAG)-binding surface in the protease. The proline-specific mutant shows high specificity for prolyl-peptidic substrate but is incapable of cleaving collagen. Engineering a GAG-binding surface on the proline-specific mutant enabled it to degrade type-I collagen in the presence of chondroitin-4-sulfate (C4-S). We also present the crystal structures of proline-specific (1.4 A) and collagen-specific (1.8 A) mutants. Finally docking studies with prolyl-peptidic substrate (Ala-Gly-Pro-Arg-Ala) at the active site and a C4-S molecule at the GAG-binding site enable us to identify key structural features responsible for collagenolytic activity of cysteine cathepsins.

Structure-guided protein engineering of human cathepsin L for efficient collagenolytic activity.,Choudhury D, Biswas S Protein Eng Des Sel. 2021 Feb 15;34. pii: 6213762. doi: 10.1093/protein/gzab005. PMID:33825882<ref>PMID:33825882</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 6jd8" style="background-color:#fffaf0;"></div>

==See Also==
*[[Cathepsin 3D structures|Cathepsin 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Biswas S]]
[[Category: Choudhury D]]