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[[Image:4esr.png|left|200px]]
==Molecular and Structural Characterization of the SH3 Domain of AHI-1 in Regulation of Cellular Resistance of BCR-ABL+ Chronic Myeloid Leukemia Cells to Tyrosine Kinase Inhibitors==
<StructureSection load='4esr' size='340' side='right' caption='[[4esr]], [[Resolution|resolution]] 1.53&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[4esr]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4ESR OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4ESR FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</scene></td></tr>
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">AHI1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</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=4esr FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4esr OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4esr RCSB], [http://www.ebi.ac.uk/pdbsum/4esr PDBsum]</span></td></tr>
</table>
== Disease ==
[[http://www.uniprot.org/uniprot/AHI1_HUMAN AHI1_HUMAN]] Joubert syndrome;Joubert syndrome with ocular defect. The disease is caused by mutations affecting the gene represented in this entry.
== Function ==
[[http://www.uniprot.org/uniprot/AHI1_HUMAN AHI1_HUMAN]] Component of the tectonic-like complex, a complex localized at the transition zone of primary cilia and acting as a barrier that prevents diffusion of transmembrane proteins between the cilia and plasma membranes.
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
ABL tyrosine kinase inhibitor (TKI) therapy induces clinical remission in chronic myeloid leukemia (CML) patients but early relapses and later emergence of TKI-resistant disease remain problematic. We recently demonstrated that the AHI-1 oncogene physically interacts with BCR-ABL and JAK2 and mediates cellular resistance to TKI in CML stem/progenitor cells. We now show that deletion of the SH3 domain of AHI-1 significantly enhances apoptotic response of BCR-ABL(+) cells to TKIs compared to cells expressing full-length AHI-1. We have also discovered a novel interaction between AHI-1 and Dynamin-2, a GTPase, through the AHI-1 SH3 domain. The crystal structure of the AHI-1 SH3 domain at 1.53-A resolution reveals that it adopts canonical SH3 folding, with the exception of an unusual C-terminal alpha helix. PD1R peptide, known to interact with the PI3K SH3 domain, was used to model the binding pattern between the AHI-1 SH3 domain and its ligands. These studies showed that an "Arg-Arg-Trp" stack may form within the binding interface, providing a potential target site for designing specific drugs. The crystal structure of the AHI-1 SH3 domain thus provides a valuable tool for identification of key interaction sites in regulation of drug resistance and for the development of small molecule inhibitors for CML.


{{STRUCTURE_4esr|  PDB=4esr  |  SCENE=  }}
Molecular and structural characterization of the SH3 domain of AHI-1 in regulation of cellular resistance of BCR-ABL(+) chronic myeloid leukemia cells To tyrosine kinase inhibitors.,Liu X, Chen M, Lobo P, An J, Grace Cheng SW, Moradian A, Morin GB, Van Petegem F, Jiang X Proteomics. 2012 May 24. doi: 10.1002/pmic.201100553. PMID:22623184<ref>PMID:22623184</ref>


===Molecular and Structural Characterization of the SH3 Domain of AHI-1 in Regulation of Cellular Resistance of BCR-ABL+ Chronic Myeloid Leukemia Cells to Tyrosine Kinase Inhibitors===
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 
</div>
{{ABSTRACT_PUBMED_22623184}}
== References ==
 
<references/>
==About this Structure==
__TOC__
[[4esr]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4ESR OCA].
</StructureSection>
 
==Reference==
<ref group="xtra">PMID:022623184</ref><references group="xtra"/>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: Jiang, X.]]
[[Category: Jiang, X]]
[[Category: Liu, P X.]]
[[Category: Liu, P X]]
[[Category: Lobo, P.]]
[[Category: Lobo, P]]
[[Category: Petegem, X F.Van.]]
[[Category: Petegem, X F.Van]]
[[Category: Ahi-1]]
[[Category: Ahi-1]]
[[Category: Ahi-1 sh3 domain]]
[[Category: Ahi-1 sh3 domain]]
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