1qvn

<table><tr><td colspan='2'>[[1qvn]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1QVN OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1QVN FirstGlance]. <br>

</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=FRI:2-GUANIDINO-4-METHYL-PENTANOIC+ACID+[2-(4-{5-[4-(4-ACETYLAMINO-BENZYLOXY)-2,3-DICHLORO-PHENYL]-2-METHYL-2H-PYRAZOL-3-YL}-PIPERIDIN-1-YL)-2-OXO-ETHYL]-AMIDE'>FRI</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>

<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">IL2 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>

[[https://www.uniprot.org/uniprot/IL2_HUMAN IL2_HUMAN]] Note=A chromosomal aberration involving IL2 is found in a form of T-cell acute lymphoblastic leukemia (T-ALL). Translocation t(4;16)(q26;p13) with involves TNFRSF17.

[[https://www.uniprot.org/uniprot/IL2_HUMAN IL2_HUMAN]] Produced by T-cells in response to antigenic or mitogenic stimulation, this protein is required for T-cell proliferation and other activities crucial to regulation of the immune response. Can stimulate B-cells, monocytes, lymphokine-activated killer cells, natural killer cells, and glioma cells.

<div style="background-color:#fffaf0;">

== Publication Abstract from PubMed ==

Protein-protein complexes remain enticing, but extremely challenging, targets for small-molecule drug discovery. In a rare example described earlier, a high-affinity small molecule, SP4206 (Kd approximately 70 nM), was found to block binding of the IL-2alpha receptor (IL-2Ralpha) to IL-2 (Kd approximately 10 nM). Recently, the structure of the IL-2/IL-2Ralpha complex was solved [Rickert, M., Wang, X., Boulanger, M. J., Goriatcheva, N., Garcia, K. C. (2005) Science 308:1477-1480]. Using structural and functional analysis, we compare how SP4206 mimics the 83-fold larger IL-2Ralpha in binding IL-2. The binding free energy per contact atom (ligand efficiency) for SP4206 is about twice that of the receptor because of a smaller, but overlapping, contact epitope that insinuates into grooves and cavities not accessed by the receptor. Despite its independent design, the small molecule has a similar, but more localized, charge distribution compared with IL-2Ralpha. Mutational studies show that SP4206 targets virtually the same critical "hot-spot" residues on IL-2 that drive binding of IL-2Ralpha. Moreover, a mutation that enhances binding to the IL-2Ralpha near these hot spots also enhances binding to SP4206. Although the protein and small molecule do bind the same hot spot, they trap very different conformations of IL-2 because of its flexible nature. Our studies suggest that precise structural mimics of receptors are not required for high-affinity binding of small molecules, and they show that there are multiple solutions to tight binding at shared and adaptive hot spots.

Hot-spot mimicry of a cytokine receptor by a small molecule.,Thanos CD, DeLano WL, Wells JA Proc Natl Acad Sci U S A. 2006 Oct 17;103(42):15422-7. Epub 2006 Oct 10. PMID:17032757<ref>PMID:17032757</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>

</div>

<div class="pdbe-citations 1qvn" style="background-color:#fffaf0;"></div>

== References ==

<references/>

[[Category: Human]]

[[Category: Delano, W L]]

[[Category: Thanos, C D]]

[[Category: Wells, J A]]

[[Category: Il-2 small molecule hot spot]]