4fxy
From Proteopedia
(Difference between revisions)
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== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[4fxy]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4FXY OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4FXY FirstGlance]. <br> | <table><tr><td colspan='2'>[[4fxy]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4FXY OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4FXY FirstGlance]. <br> | ||
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=0W2:1-{(2S)-1-[(3R)-3-(2-CHLOROPHENYL)-2-(2-FLUOROPHENYL)PYRAZOLIDIN-1-YL]-1-OXOPROPAN-2-YL}-3-[(1R,3S,5R,7R)-TRICYCLO[3.3.1.1~3,7~]DEC-2-YL]UREA'>0W2</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</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]] 2.8Å</td></tr> |
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=0W2:1-{(2S)-1-[(3R)-3-(2-CHLOROPHENYL)-2-(2-FLUOROPHENYL)PYRAZOLIDIN-1-YL]-1-OXOPROPAN-2-YL}-3-[(1R,3S,5R,7R)-TRICYCLO[3.3.1.1~3,7~]DEC-2-YL]UREA'>0W2</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</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=4fxy FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4fxy OCA], [https://pdbe.org/4fxy PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4fxy RCSB], [https://www.ebi.ac.uk/pdbsum/4fxy PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4fxy 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=4fxy FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4fxy OCA], [https://pdbe.org/4fxy PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4fxy RCSB], [https://www.ebi.ac.uk/pdbsum/4fxy PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4fxy ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Function == | == Function == | ||
[https://www.uniprot.org/uniprot/NEUL_RAT NEUL_RAT] Hydrolyzes oligopeptides such as neurotensin, bradykinin and dynorphin A. | [https://www.uniprot.org/uniprot/NEUL_RAT NEUL_RAT] Hydrolyzes oligopeptides such as neurotensin, bradykinin and dynorphin A. | ||
| - | <div style="background-color:#fffaf0;"> | ||
| - | == Publication Abstract from PubMed == | ||
| - | Neuropeptidases specialize in the hydrolysis of the small bioactive peptides that play a variety of signaling roles in the nervous and endocrine systems. One neuropeptidase, neurolysin, helps control the levels of the dopaminergic circuit modulator neurotensin and is a member of a fold group that includes the antihypertensive target angiotensin converting enzyme. We report the discovery of a potent inhibitor that, unexpectedly, binds away from the enzyme catalytic site. The location of the bound inhibitor suggests it disrupts activity by preventing a hinge-like motion associated with substrate binding and catalysis. In support of this model, the inhibition kinetics are mixed, with both noncompetitive and competitive components, and fluorescence polarization shows directly that the inhibitor reverses a substrate-associated conformational change. This new type of inhibition may have widespread utility in targeting neuropeptidases. | ||
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| - | Allosteric Inhibition of the Neuropeptidase Neurolysin.,Hines CS, Ray K, Schmidt JJ, Xiong F, Feenstra RW, Pras-Raves M, de Moes JP, Lange JH, Melikishvili M, Fried MG, Mortenson P, Charlton M, Patel Y, Courtney SM, Kruse CG, Rodgers DW J Biol Chem. 2014 Nov 5. pii: jbc.M114.620930. PMID:25378390<ref>PMID:25378390</ref> | ||
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| - | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| - | </div> | ||
| - | <div class="pdbe-citations 4fxy" style="background-color:#fffaf0;"></div> | ||
| - | == References == | ||
| - | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
Current revision
Crystal structure of rat neurolysin with bound pyrazolidin inhibitor
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