5om2: Difference between revisions
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==Crystal structure of Alpha1-antichymotrypsin variant DBS-I1: a drug-binding serpin for doxycycline== | ==Crystal structure of Alpha1-antichymotrypsin variant DBS-I1: a drug-binding serpin for doxycycline== | ||
<StructureSection load='5om2' size='340' side='right' caption='[[5om2]], [[Resolution|resolution]] 1.47Å' scene=''> | <StructureSection load='5om2' size='340' side='right'caption='[[5om2]], [[Resolution|resolution]] 1.47Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[5om2]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5OM2 OCA]. For a <b>guided tour on the structure components</b> use [ | <table><tr><td colspan='2'>[[5om2]] 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=5OM2 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5OM2 FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=DXT:(4S,4AR,5S,5AR,6R,12AS)-4-(DIMETHYLAMINO)-3,5,10,12,12A-PENTAHYDROXY-6-METHYL-1,11-DIOXO-1,4,4A,5,5A,6,11,12A-OCTAHYDROTETRACENE-2-CARBOXAMIDE'>DXT</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</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]] 1.47Å</td></tr> | ||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=DXT:(4S,4AR,5S,5AR,6R,12AS)-4-(DIMETHYLAMINO)-3,5,10,12,12A-PENTAHYDROXY-6-METHYL-1,11-DIOXO-1,4,4A,5,5A,6,11,12A-OCTAHYDROTETRACENE-2-CARBOXAMIDE'>DXT</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</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=5om2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5om2 OCA], [https://pdbe.org/5om2 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5om2 RCSB], [https://www.ebi.ac.uk/pdbsum/5om2 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5om2 ProSAT]</span></td></tr> | |||
</table> | </table> | ||
== Function == | == Function == | ||
[ | [https://www.uniprot.org/uniprot/AACT_HUMAN AACT_HUMAN] Although its physiological function is unclear, it can inhibit neutrophil cathepsin G and mast cell chymase, both of which can convert angiotensin-1 to the active angiotensin-2.<ref>PMID:2404007</ref> | ||
<div style="background-color:#fffaf0;"> | <div style="background-color:#fffaf0;"> | ||
== Publication Abstract from PubMed == | == Publication Abstract from PubMed == | ||
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</div> | </div> | ||
<div class="pdbe-citations 5om2" style="background-color:#fffaf0;"></div> | <div class="pdbe-citations 5om2" style="background-color:#fffaf0;"></div> | ||
==See Also== | |||
*[[Serpin 3D structures|Serpin 3D structures]] | |||
== References == | == References == | ||
<references/> | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: | [[Category: Homo sapiens]] | ||
[[Category: | [[Category: Large Structures]] | ||
[[Category: | [[Category: Muller YA]] | ||
[[Category: | [[Category: Schmidt K]] | ||
Latest revision as of 19:54, 13 December 2023
Crystal structure of Alpha1-antichymotrypsin variant DBS-I1: a drug-binding serpin for doxycyclineCrystal structure of Alpha1-antichymotrypsin variant DBS-I1: a drug-binding serpin for doxycycline
Structural highlights
FunctionAACT_HUMAN Although its physiological function is unclear, it can inhibit neutrophil cathepsin G and mast cell chymase, both of which can convert angiotensin-1 to the active angiotensin-2.[1] Publication Abstract from PubMedThe allosteric interplay between distant functional sites present in a single protein provides for one of the most important regulatory mechanisms in biological systems. While the design of ligand-binding sites into proteins remains challenging, this holds even truer for the coupling of a newly engineered binding site to an allosteric mechanism that regulates the ligand affinity. Here it is shown how computational design algorithms enabled the introduction of doxycycline- and doxorubicin-binding sites into the serine proteinase inhibitor (serpin) family member alpha1-antichymotrypsin. Further engineering allowed exploitation of the proteinase-triggered serpin-typical S-to-R transition to modulate the ligand affinities. These design variants follow strategies observed in naturally occurring plasma globulins that allow for the targeted delivery of hormones in the blood. By analogy, we propose that the variants described in the present study could be further developed to allow for the delivery of the antibiotic doxycycline and the anticancer compound doxorubicin to tissues/locations that express specific proteinases, such as bacterial infection sites or tumor cells secreting matrix metalloproteinases. Design of an allosterically modulated doxycycline and doxorubicin drug-binding protein.,Schmidt K, Gardill BR, Kern A, Kirchweger P, Borsch M, Muller YA Proc Natl Acad Sci U S A. 2018 May 14. pii: 1716666115. doi:, 10.1073/pnas.1716666115. PMID:29760101[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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