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[[Image:2q5a.png|left|200px]]


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==human Pin1 bound to L-PEPTIDE==
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<StructureSection load='2q5a' size='340' side='right'caption='[[2q5a]], [[Resolution|resolution]] 1.50&Aring;' scene=''>
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== Structural highlights ==
or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
<table><tr><td colspan='2'>[[2q5a]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. This structure supersedes the now removed PDB entry [http://oca.weizmann.ac.il/oca-bin/send-pdb?obs=1&id=2iti 2iti]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2Q5A OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2Q5A FirstGlance]. <br>
or leave the SCENE parameter empty for the default display.
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=16P:3,6,9,12,15,18-HEXAOXAICOSANE'>16P</scene></td></tr>
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<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=ACE:ACETYL+GROUP'>ACE</scene>, <scene name='pdbligand=NAL:BETA-(2-NAPHTHYL)-ALANINE'>NAL</scene>, <scene name='pdbligand=NH2:AMINO+GROUP'>NH2</scene>, <scene name='pdbligand=TPO:PHOSPHOTHREONINE'>TPO</scene>, <scene name='pdbligand=YCP:(2S)-PIPERIDINE-2-CARBOXYLIC+ACID'>YCP</scene></td></tr>
{{STRUCTURE_2q5a|  PDB=2q5a  |  SCENE= }}
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[2itk|2itk]], [[1pin|1pin]]</div></td></tr>
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">PIN1 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Peptidylprolyl_isomerase Peptidylprolyl isomerase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=5.2.1.8 5.2.1.8] </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=2q5a FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2q5a OCA], [https://pdbe.org/2q5a PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2q5a RCSB], [https://www.ebi.ac.uk/pdbsum/2q5a PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2q5a ProSAT]</span></td></tr>
</table>
== Function ==
[[https://www.uniprot.org/uniprot/PIN1_HUMAN PIN1_HUMAN]] Essential PPIase that regulates mitosis presumably by interacting with NIMA and attenuating its mitosis-promoting activity. Displays a preference for an acidic residue N-terminal to the isomerized proline bond. Catalyzes pSer/Thr-Pro cis/trans isomerizations. Down-regulates kinase activity of BTK. Can transactivate multiple oncogenes and induce centrosome amplification, chromosome instability and cell transformation. Required for the efficient dephosphorylation and recycling of RAF1 after mitogen activation.<ref>PMID:15664191</ref> <ref>PMID:16644721</ref> <ref>PMID:21497122</ref> 
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
Check<jmol>
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    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/q5/2q5a_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/main_output.php?pdb_ID=2q5a ConSurf].
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== Publication Abstract from PubMed ==
Human Pin1 is a key regulator of cell-cycle progression and plays growth-promoting roles in human cancers. High-affinity inhibitors of Pin1 may provide a unique opportunity for disrupting oncogenic pathways. Here we report two high-resolution X-ray crystal structures of human Pin1 bound to non-natural peptide inhibitors. The structures of the bound high-affinity peptides identify a type-I beta-turn conformation for Pin1 prolyl peptide isomerase domain-peptide binding and an extensive molecular interface for high-affinity recognition. Moreover, these structures suggest chemical elements that may further improve the affinity and pharmacological properties of future peptide-based Pin inhibitors. Finally, an intramolecular hydrogen bond observed in both peptide complexes mimics the cyclic conformation of FK506 and rapamycin. Both FK506 and rapamycin are clinically important inhibitors of other peptidyl-prolyl cis-trans isomerases. This comparative discovery suggests that a cyclic peptide polyketide bridge, like that found in FK506 and rapamycin or a similar linkage, may significantly improve the binding affinity of structure-based Pin1 inhibitors.


===human Pin1 bound to L-PEPTIDE===
Structural basis for high-affinity peptide inhibition of human Pin1.,Zhang Y, Daum S, Wildemann D, Zhou XZ, Verdecia MA, Bowman ME, Lucke C, Hunter T, Lu KP, Fischer G, Noel JP ACS Chem Biol. 2007 May 22;2(5):320-8. PMID:17518432<ref>PMID:17518432</ref>


From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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==See Also==
The line below this paragraph, {{ABSTRACT_PUBMED_17518432}}, adds the Publication Abstract to the page
*[[Peptidyl-prolyl cis-trans isomerase 3D structures|Peptidyl-prolyl cis-trans isomerase 3D structures]]
(as it appears on PubMed at http://www.pubmed.gov), where 17518432 is the PubMed ID number.
== References ==
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<references/>
{{ABSTRACT_PUBMED_17518432}}
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</StructureSection>
==About this Structure==
[[Category: Human]]
2Q5A is a 2 chains structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. This structure supersedes the now removed PDB entry [http://oca.weizmann.ac.il/oca-bin/send-pdb?obs=1&id=2iti 2iti]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2Q5A OCA].
[[Category: Large Structures]]
 
==Reference==
<ref group="xtra">PMID:17518432</ref><references group="xtra"/>
[[Category: Homo sapiens]]
[[Category: Peptidylprolyl isomerase]]
[[Category: Peptidylprolyl isomerase]]
[[Category: Noel, J P.]]
[[Category: Noel, J P]]
[[Category: Zhang, Y.]]
[[Category: Zhang, Y]]
[[Category: Isomerase ww domain]]
[[Category: Isomerase ww domain]]
 
[[Category: Isomerase-isomerase inhibitor complex]]
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