View source for 5om5


==Crystal structure of Alpha1-antichymotrypsin variant DBS-I-allo1: an allosterically triggered drug-binding serpin for doxycycline==
<StructureSection load='5om5' size='340' side='right'caption='[[5om5]], [[Resolution|resolution]] 1.59&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[5om5]] 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=5OM5 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5OM5 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]] 1.595&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</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=5om5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5om5 OCA], [https://pdbe.org/5om5 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5om5 RCSB], [https://www.ebi.ac.uk/pdbsum/5om5 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5om5 ProSAT]</span></td></tr>
</table>
== 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;">
== Publication Abstract from PubMed ==
The 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<ref>PMID:29760101</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 5om5" style="background-color:#fffaf0;"></div>

==See Also==
*[[Serpin 3D structures|Serpin 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Muller YA]]
[[Category: Schmidt K]]