View source for 8ozz


==PH domain of AKT-like kinase in Trypanosoma cruzi==
<StructureSection load='8ozz' size='340' side='right'caption='[[8ozz]]' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[8ozz]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Trypanosoma_cruzi Trypanosoma cruzi]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8OZZ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8OZZ FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR</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=8ozz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8ozz OCA], [https://pdbe.org/8ozz PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8ozz RCSB], [https://www.ebi.ac.uk/pdbsum/8ozz PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8ozz ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/Q4D6D3_TRYCC Q4D6D3_TRYCC] 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
According to the World Health Organization, Chagas disease (CD) is the most prevalent poverty-promoting neglected tropical disease. Alarmingly, climate change is accelerating the geographical spreading of CD causative parasite, Trypanosoma cruzi, which additionally increases infection rates. Still, CD treatment remains challenging due to a lack of safe and efficient drugs. In this work, we analyze the viability of T. cruzi Akt-like kinase (TcAkt) as drug target against CD including primary structural and functional information about a parasitic Akt protein. Nuclear Magnetic Resonance derived information in combination with Molecular Dynamics simulations offer detailed insights into structural properties of the pleckstrin homology (PH) domain of TcAkt and its binding to phosphatidylinositol phosphate ligands (PIP). Experimental data combined with Alpha Fold proposes a model for the mechanism of action of TcAkt involving a PIP-induced disruption of the intramolecular interface between the kinase and the PH domain resulting in an open conformation enabling TcAkt kinase activity. Further docking experiments reveal that TcAkt is recognized by human inhibitors PIT-1 and capivasertib, and TcAkt inhibition by UBMC-4 and UBMC-6 is achieved via binding to TcAkt kinase domain. Our in-depth structural analysis of TcAkt reveals potential sites for drug development against CD, located at activity essential regions.

Structural investigation of Trypanosoma cruzi Akt-like kinase as drug target against Chagas disease.,Stadler KA, Ortiz-Joya LJ, Singh Sahrawat A, Buhlheller C, Gruber K, Pavkov-Keller T, O'Hagan TB, Guarne A, Pulido S, Marin-Villa M, Zangger K, Gubensak N Sci Rep. 2024 May 2;14(1):10039. doi: 10.1038/s41598-024-59654-8. PMID:38693166<ref>PMID:38693166</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 8ozz" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Trypanosoma cruzi]]
[[Category: Gubensaek N]]
[[Category: Ortiz-Joya LJ]]
[[Category: Stadler KA]]
[[Category: Zangger K]]