View source for 9puk


==Neutralizing monoclonal antibody Fab fragment for human leptin==
<StructureSection load='9puk' size='340' side='right'caption='[[9puk]], [[Resolution|resolution]] 3.30&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[9puk]] is a 4 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=9PUK OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=9PUK 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]] 3.3&#8491;</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=9puk FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=9puk OCA], [https://pdbe.org/9puk PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=9puk RCSB], [https://www.ebi.ac.uk/pdbsum/9puk PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=9puk ProSAT]</span></td></tr>
</table>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Leptin, a hormone primarily secreted by adipocytes, regulates energy balance and systemic metabolism through its interaction with the leptin receptor (LEPR). Beyond these functions, leptin signaling has been implicated in the pathogenesis of tissue fibrosis. Here, we report the x-ray crystal structures of a leptin-neutralizing antibody (hLep3) in the unbound and leptin-bound states. The interaction of this antibody with leptin mimics the interaction of the LEPR with leptin, providing direct insights into the mechanism by which the antibody disrupts leptin signaling. We furthermore evaluate the therapeutic potential of neutralizing leptin with this antibody across distinct mouse models of fibrosis affecting the kidney, liver, lung, heart, and blood vessels. Leptin neutralization markedly inhibited fibrosis progression in all models. Mechanistically, suppression of leptin activity reduces pro-inflammatory and profibrotic processes, underscoring its therapeutic potential. These findings suggest that leptin signaling plays a vital role in tissue fibrosis and that treatment with a leptin-neutralizing antibody may be a promising therapeutic approach.

Leptin as a key driver for organ fibrogenesis.,Sun XN, Chen S, Zhao S, Funcke JB, Virostek M, Pedersen L, Li C, Joung C, Lin Q, Li Y, Cobb A, Wang MY, Min K, Maya-Ramos L, Degasperi G, Liu J, Zhang N, An Z, Tomchick DR, Wynn RM, Oh DY, Scherer PE Sci Adv. 2025 Oct 24;11(43):eady7904. doi: 10.1126/sciadv.ady7904. Epub 2025 Oct , 22. PMID:41124259<ref>PMID:41124259</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 9puk" style="background-color:#fffaf0;"></div>
== References ==
<references/>
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Scherer PE]]
[[Category: Tomchick DR]]
[[Category: Wynn RM]]