1mik
From Proteopedia
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| - | [[ | + | ==THE ROLE OF WATER MOLECULES IN THE STRUCTURE-BASED DESIGN OF (5-HYDROXYNORVALINE)-2-CYCLOSPORIN: SYNTHESIS, BIOLOGICAL ACTIVITY, AND CRYSTALLOGRAPHIC ANALYSIS WITH CYCLOPHILIN A== |
| + | <StructureSection load='1mik' size='340' side='right' caption='[[1mik]], [[Resolution|resolution]] 1.76Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[1mik]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1MIK OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1MIK FirstGlance]. <br> | ||
| + | </td></tr><tr><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=AA4:2-AMINO-5-HYDROXYPENTANOIC+ACID'>AA4</scene>, <scene name='pdbligand=BMT:4-METHYL-4-[(E)-2-BUTENYL]-4,N-METHYL-THREONINE'>BMT</scene>, <scene name='pdbligand=DAL:D-ALANINE'>DAL</scene>, <scene name='pdbligand=MLE:N-METHYLLEUCINE'>MLE</scene>, <scene name='pdbligand=MVA:N-METHYLVALINE'>MVA</scene>, <scene name='pdbligand=SAR:SARCOSINE'>SAR</scene></td></tr> | ||
| + | <tr><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1bck|1bck]], [[1c5f|1c5f]], [[1csa|1csa]], [[1cwa|1cwa]], [[1cwb|1cwb]], [[1cwc|1cwc]], [[1cwf|1cwf]], [[1cwh|1cwh]], [[1cwi|1cwi]], [[1cwj|1cwj]], [[1cwk|1cwk]], [[1cwl|1cwl]], [[1cwm|1cwm]], [[1cwo|1cwo]], [[1cya|1cya]], [[1cyb|1cyb]], [[1cyn|1cyn]], [[1ikf|1ikf]], [[1m63|1m63]], [[1mf8|1mf8]], [[1qng|1qng]], [[1qnh|1qnh]], [[1xq7|1xq7]], [[2esl|2esl]], [[2oju|2oju]], [[2poy|2poy]], [[2rma|2rma]], [[2rmb|2rmb]], [[2rmc|2rmc]], [[2wfj|2wfj]], [[2x2c|2x2c]], [[2x7k|2x7k]], [[2z6w|2z6w]], [[3bo7|3bo7]], [[3cys|3cys]], [[3eov|3eov]]</td></tr> | ||
| + | <tr><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">CYCLOPHILIN ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</td></tr> | ||
| + | <tr><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Peptidylprolyl_isomerase Peptidylprolyl isomerase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=5.2.1.8 5.2.1.8] </span></td></tr> | ||
| + | <tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1mik FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1mik OCA], [http://www.rcsb.org/pdb/explore.do?structureId=1mik RCSB], [http://www.ebi.ac.uk/pdbsum/1mik PDBsum]</span></td></tr> | ||
| + | <table> | ||
| + | == Evolutionary Conservation == | ||
| + | [[Image:Consurf_key_small.gif|200px|right]] | ||
| + | Check<jmol> | ||
| + | <jmolCheckbox> | ||
| + | <scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/mi/1mik_consurf.spt"</scriptWhenChecked> | ||
| + | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | ||
| + | <text>to colour the structure by Evolutionary Conservation</text> | ||
| + | </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/chain_selection.php?pdb_ID=2ata ConSurf]. | ||
| + | <div style="clear:both"></div> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Analysis of the contact surface of the cyclophilin A (CypA)/cyclosporin A (CsA, 1) crystal structure delineates a unique cavity between both molecules in the vicinity of the Abu-2 side chain atoms of 1 (Abu pocket). Therefore, (5-hydroxynorvaline)-2-cyclosporin (2) was designed and prepared as a CsA derivative which could mediate additional interactions within the pocket. The X-ray crystal structure of the CypA/2 complex at 1.76 A resolution shows that 1 and 2 have identical backbone conformations and that the introduced hydroxypropyl chain makes indeed the expected supplemental interactions with CypA. However, 2 has 8-9-fold lower binding affinity than 1 for CypA. This results from a presumed unfavorable free energy change associated with the displacement of one of the tightly bound water molecules within the pocket and a change in prebinding equilibria. The role of the later was assessed by comparing the conformation distribution of 1 and 2 to that of norvaline-2-cyclosporin (3) and norvaline-2-(D-MeSer)-3-cyclosporin (4). | ||
| - | + | The role of water molecules in the structure-based design of (5-hydroxynorvaline)-2-cyclosporin: synthesis, biological activity, and crystallographic analysis with cyclophilin A.,Mikol V, Papageorgiou C, Borer X J Med Chem. 1995 Aug 18;38(17):3361-7. PMID:7650689<ref>PMID:7650689</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | + | </div> | |
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==See Also== | ==See Also== | ||
*[[Cyclophilin|Cyclophilin]] | *[[Cyclophilin|Cyclophilin]] | ||
| - | + | == References == | |
| - | == | + | <references/> |
| - | < | + | __TOC__ |
| + | </StructureSection> | ||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Peptidylprolyl isomerase]] | [[Category: Peptidylprolyl isomerase]] | ||
Revision as of 15:24, 28 September 2014
THE ROLE OF WATER MOLECULES IN THE STRUCTURE-BASED DESIGN OF (5-HYDROXYNORVALINE)-2-CYCLOSPORIN: SYNTHESIS, BIOLOGICAL ACTIVITY, AND CRYSTALLOGRAPHIC ANALYSIS WITH CYCLOPHILIN A
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