View source for 9puo


==Neutralizing monoclonal antibody Fab fragment bound to leptin==
<StructureSection load='9puo' size='340' side='right'caption='[[9puo]], [[Resolution|resolution]] 3.10&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[9puo]] is a 6 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=9PUO OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=9PUO 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]] 3.1&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</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=9puo FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=9puo OCA], [https://pdbe.org/9puo PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=9puo RCSB], [https://www.ebi.ac.uk/pdbsum/9puo PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=9puo ProSAT]</span></td></tr>
</table>
== Disease ==
[https://www.uniprot.org/uniprot/LEP_HUMAN LEP_HUMAN] Defects in LEP may be a cause of obesity (OBESITY) [MIM:[https://omim.org/entry/601665 601665]. It is a condition characterized by an increase of body weight beyond the limitation of skeletal and physical requirements, as the result of excessive accumulation of body fat.<ref>PMID:9500540</ref> 
== Function ==
[https://www.uniprot.org/uniprot/LEP_HUMAN LEP_HUMAN] May function as part of a signaling pathway that acts to regulate the size of the body fat depot. An increase in the level of LEP may act directly or indirectly on the CNS to inhibit food intake and/or regulate energy expenditure as part of a homeostatic mechanism to maintain constancy of the adipose mass.
<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 9puo" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Scherer PE]]
[[Category: Tomchick DR]]
[[Category: Wynn RM]]