1qr3: Difference between revisions
No edit summary |
No edit summary |
||
| (4 intermediate revisions by the same user not shown) | |||
| Line 1: | Line 1: | ||
==Structure of porcine pancreatic elastase in complex with FR901277, a novel macrocyclic inhibitor of elastases at 1.6 angstrom resolution== | ==Structure of porcine pancreatic elastase in complex with FR901277, a novel macrocyclic inhibitor of elastases at 1.6 angstrom resolution== | ||
<StructureSection load='1qr3' size='340' side='right' caption='[[1qr3]], [[Resolution|resolution]] 1.60Å' scene=''> | <StructureSection load='1qr3' size='340' side='right'caption='[[1qr3]], [[Resolution|resolution]] 1.60Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[1qr3]] is a 2 chain structure with sequence from [ | <table><tr><td colspan='2'>[[1qr3]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Streptomyces_resistomycificus Streptomyces resistomycificus] and [https://en.wikipedia.org/wiki/Sus_scrofa Sus scrofa]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1QR3 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1QR3 FirstGlance]. <br> | ||
</td></tr><tr id=' | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.6Å</td></tr> | ||
<tr id=' | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ALQ:2-METHYL-PROPIONIC+ACID'>ALQ</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=CIR:CITRULLINE'>CIR</scene>, <scene name='pdbligand=DBU:(2Z)-2-AMINOBUT-2-ENOIC+ACID'>DBU</scene>, <scene name='pdbligand=GLJ:5,5-DIHYDROXY-L-NORVALINE'>GLJ</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=TYJ:2,5-DIHYDROXY-N-METHYL-L-TYROSINE'>TYJ</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=1qr3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1qr3 OCA], [https://pdbe.org/1qr3 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1qr3 RCSB], [https://www.ebi.ac.uk/pdbsum/1qr3 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1qr3 ProSAT]</span></td></tr> | |||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | |||
</table> | </table> | ||
== Function == | == Function == | ||
[ | [https://www.uniprot.org/uniprot/CELA1_PIG CELA1_PIG] Acts upon elastin. | ||
== Evolutionary Conservation == | == Evolutionary Conservation == | ||
[[Image:Consurf_key_small.gif|200px|right]] | [[Image:Consurf_key_small.gif|200px|right]] | ||
Check<jmol> | Check<jmol> | ||
<jmolCheckbox> | <jmolCheckbox> | ||
<scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/qr/1qr3_consurf.spt"</scriptWhenChecked> | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/qr/1qr3_consurf.spt"</scriptWhenChecked> | ||
<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | ||
<text>to colour the structure by Evolutionary Conservation</text> | <text>to colour the structure by Evolutionary Conservation</text> | ||
</jmolCheckbox> | </jmolCheckbox> | ||
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/ | </jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=1qr3 ConSurf]. | ||
<div style="clear:both"></div> | <div style="clear:both"></div> | ||
<div style="background-color:#fffaf0;"> | <div style="background-color:#fffaf0;"> | ||
| Line 28: | Line 28: | ||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
</div> | </div> | ||
<div class="pdbe-citations 1qr3" style="background-color:#fffaf0;"></div> | |||
==See Also== | ==See Also== | ||
*[[Elastase|Elastase]] | *[[Elastase 3D structures|Elastase 3D structures]] | ||
== References == | == References == | ||
<references/> | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: | [[Category: Large Structures]] | ||
[[Category: Streptomyces resistomycificus]] | [[Category: Streptomyces resistomycificus]] | ||
[[Category: Sus scrofa]] | [[Category: Sus scrofa]] | ||
[[Category: Kinoshita | [[Category: Kinoshita T]] | ||
[[Category: Nakanishi | [[Category: Nakanishi I]] | ||
[[Category: Sato | [[Category: Sato A]] | ||
[[Category: Tada | [[Category: Tada T]] | ||
Latest revision as of 11:02, 15 November 2023
Structure of porcine pancreatic elastase in complex with FR901277, a novel macrocyclic inhibitor of elastases at 1.6 angstrom resolutionStructure of porcine pancreatic elastase in complex with FR901277, a novel macrocyclic inhibitor of elastases at 1.6 angstrom resolution
Structural highlights
FunctionCELA1_PIG Acts upon elastin. Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedHuman leukocyte elastase (HLE) is a serine protease that contributes to tissue destruction in various disease states-for example, in emphysema. FR901277 is a natural product isolated from the culture filtrate of Streptomyces resistomicificus and is a potent inhibitor of both HLE and porcine pancreatic elastase (PPE). FR901277 consists of four normal amino acids and three unusual amino acids, and is a unique bicyclic peptide compound. The crystal structure of PPE complexed with FR901277 has been determined at 1.6 A resolution. The Ogamma atom of Ser-195 in PPE did not form a covalent bond with FR901277, but formed a hydrogen bond with the Nvarepsilon atom of His-57. On the other hand, the portion from L-Orn(1) through dehydroxyThr(3) in FR901277 formed an antiparallel beta-sheet structure with the backbone of the active site in PPE. The S4 through S2' binding subsites in PPE were all occupied by the hydrophobic side chains of the inhibitor molecule. Especially, the ethylidene moiety of FR901277 occupied the S1 specific pocket, indicating a CH/pi interaction. In addition, the isopropyl side chain of L-Val(7) was located at the enzyme surface between the S2 and S1' pockets with several van der Waals contacts. However, the amino acid (4) residue was not involved in a significant interaction with PPE. Comparison of inhibitor structures in different environments showed that FR901277 has a highly rigid bicyclic framework; however, it can slightly change its conformation according to the circumstances. The binding mode of FR901277 at the active site of PPE was directly applicable to that in HLE, after consideration of induced fit. The structure of the PPE-FR901277 complex provided much information regarding potential sites for modification of the physicochemical properties of FR901277. Structure of porcine pancreatic elastase complexed with FR901277, a novel macrocyclic inhibitor of elastases, at 1.6 A resolution.,Nakanishi I, Kinoshita T, Sato A, Tada T Biopolymers. 2000 Apr 15;53(5):434-45. PMID:10738204[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
|
| ||||||||||||||||||