4mnx: Difference between revisions
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== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[4mnx]] is a 2 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=4MNX OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4MNX FirstGlance]. <br> | <table><tr><td colspan='2'>[[4mnx]] is a 2 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=4MNX OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4MNX FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=29N:1,1,1-(1,3,5-TRIAZINANE-1,3,5-TRIYL)TRIPROPAN-1-ONE'>29N</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=NH2:AMINO+GROUP'>NH2</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr> | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.85Å</td></tr> | ||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=29N:1,1,1-(1,3,5-TRIAZINANE-1,3,5-TRIYL)TRIPROPAN-1-ONE'>29N</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=NH2:AMINO+GROUP'>NH2</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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=4mnx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4mnx OCA], [https://pdbe.org/4mnx PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4mnx RCSB], [https://www.ebi.ac.uk/pdbsum/4mnx PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4mnx ProSAT]</span></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=4mnx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4mnx OCA], [https://pdbe.org/4mnx PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4mnx RCSB], [https://www.ebi.ac.uk/pdbsum/4mnx PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4mnx ProSAT]</span></td></tr> | ||
</table> | </table> | ||
Latest revision as of 13:17, 30 October 2024
Crystal structure of urokinase-type plasminogen activator (uPA) complexed with bicyclic peptide UK811Crystal structure of urokinase-type plasminogen activator (uPA) complexed with bicyclic peptide UK811
Structural highlights
DiseaseUROK_HUMAN Defects in PLAU are the cause of Quebec platelet disorder (QPD) [MIM:601709. QPD is an autosomal dominant bleeding disorder due to a gain-of-function defect in fibrinolysis. Although affected individuals do not exhibit systemic fibrinolysis, they show delayed onset bleeding after challenge, such as surgery. The hallmark of the disorder is markedly increased PLAU levels within platelets, which causes intraplatelet plasmin generation and secondary degradation of alpha-granule proteins.[1] FunctionUROK_HUMAN Specifically cleaves the zymogen plasminogen to form the active enzyme plasmin. Publication Abstract from PubMedBicyclic peptides generated through directed evolution by using phage display offer an attractive ligand format for the development of therapeutics. Being nearly 100-fold smaller than antibodies, they promise advantages such as access to chemical synthesis, efficient diffusion into tissues, and needle-free application. However, unlike antibodies, they do not have a folded structure in solution and thus bind less well. We developed bicyclic peptides with hydrophilic chemical structures at their center to promote noncovalent intramolecular interactions, thereby stabilizing the peptide conformation. The sequences of the peptides isolated by phage display from large combinatorial libraries were strongly influenced by the type of small molecule used in the screen, thus suggesting that the peptides fold around the small molecules. X-ray structure analysis revealed that the small molecules indeed formed hydrogen bonds with the peptides. These noncovalent interactions stabilize the peptide-protein complexes and contribute to the high binding affinity. Peptide ligands stabilized by small molecules.,Chen S, Bertoldo D, Angelini A, Pojer F, Heinis C Angew Chem Int Ed Engl. 2014 Feb 3;53(6):1602-6. doi: 10.1002/anie.201309459., Epub 2014 Jan 22. PMID:24453110[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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