2zb8: Difference between revisions

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[[Image:2zb8.png|left|200px]]
==Crystal structure of human 15-ketoprostaglandin delta-13-reductase in complex with NADP and indomethacin==
<StructureSection load='2zb8' size='340' side='right' caption='[[2zb8]], [[Resolution|resolution]] 2.00&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[2zb8]] is a 1 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=2ZB8 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2ZB8 FirstGlance]. <br>
</td></tr><tr><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=IMN:INDOMETHACIN'>IMN</scene>, <scene name='pdbligand=NAP:NADP+NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NAP</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene><br>
<tr><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2zb3|2zb3]], [[2zb4|2zb4]], [[2zb7|2zb7]]</td></tr>
<tr><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">PTGR2, ZADH1 ([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/15-oxoprostaglandin_13-oxidase 15-oxoprostaglandin 13-oxidase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.3.1.48 1.3.1.48] </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=2zb8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2zb8 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2zb8 RCSB], [http://www.ebi.ac.uk/pdbsum/2zb8 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/zb/2zb8_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 ==
PTGR2 catalyzes an NADPH-dependent reduction of the conjugated alpha,beta-unsaturated double bond of 15-keto-PGE(2), a key step in terminal inactivation of prostaglandins and suppression of PPARgamma-mediated adipocyte differentiation. Selective inhibition of PTGR2 may contribute to the improvement of insulin sensitivity with fewer side effects. PTGR2 belongs to the medium-chain dehydrogenase/reductase superfamily. The crystal structures reported here reveal features of the NADPH binding-induced conformational change in a LID motif and a polyproline type II helix which are critical for the reaction. Mutation of Tyr64 and Tyr259 significantly reduces the rate of catalysis but increases the affinity to substrate, confirming the structural observations. Besides targeting cyclooxygenase, indomethacin also inhibits PTGR2 with a binding mode similar to that of 15-keto-PGE(2). The LID motif becomes highly disordered upon the binding of indomethacin, indicating plasticity of the active site. This study has implications for the rational design of inhibitors of PTGR2.


{{STRUCTURE_2zb8|  PDB=2zb8  |  SCENE=  }}
Structural basis for catalytic and inhibitory mechanisms of human prostaglandin reductase PTGR2.,Wu YH, Ko TP, Guo RT, Hu SM, Chuang LM, Wang AH Structure. 2008 Nov 12;16(11):1714-23. PMID:19000823<ref>PMID:19000823</ref>


===Crystal structure of human 15-ketoprostaglandin delta-13-reductase in complex with NADP and indomethacin===
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 
</div>
{{ABSTRACT_PUBMED_19000823}}
== References ==
 
<references/>
==About this Structure==
__TOC__
[[2zb8]] is a 1 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=2ZB8 OCA].
</StructureSection>
 
==Reference==
<ref group="xtra">PMID:019000823</ref><references group="xtra"/>
[[Category: 15-oxoprostaglandin 13-oxidase]]
[[Category: 15-oxoprostaglandin 13-oxidase]]
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]

Revision as of 08:36, 2 October 2014

Crystal structure of human 15-ketoprostaglandin delta-13-reductase in complex with NADP and indomethacinCrystal structure of human 15-ketoprostaglandin delta-13-reductase in complex with NADP and indomethacin

Structural highlights

2zb8 is a 1 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:, ,
Related:2zb3, 2zb4, 2zb7
Gene:PTGR2, ZADH1 (Homo sapiens)
Activity:15-oxoprostaglandin 13-oxidase, with EC number 1.3.1.48
Resources:FirstGlance, OCA, RCSB, PDBsum

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 PubMed

PTGR2 catalyzes an NADPH-dependent reduction of the conjugated alpha,beta-unsaturated double bond of 15-keto-PGE(2), a key step in terminal inactivation of prostaglandins and suppression of PPARgamma-mediated adipocyte differentiation. Selective inhibition of PTGR2 may contribute to the improvement of insulin sensitivity with fewer side effects. PTGR2 belongs to the medium-chain dehydrogenase/reductase superfamily. The crystal structures reported here reveal features of the NADPH binding-induced conformational change in a LID motif and a polyproline type II helix which are critical for the reaction. Mutation of Tyr64 and Tyr259 significantly reduces the rate of catalysis but increases the affinity to substrate, confirming the structural observations. Besides targeting cyclooxygenase, indomethacin also inhibits PTGR2 with a binding mode similar to that of 15-keto-PGE(2). The LID motif becomes highly disordered upon the binding of indomethacin, indicating plasticity of the active site. This study has implications for the rational design of inhibitors of PTGR2.

Structural basis for catalytic and inhibitory mechanisms of human prostaglandin reductase PTGR2.,Wu YH, Ko TP, Guo RT, Hu SM, Chuang LM, Wang AH Structure. 2008 Nov 12;16(11):1714-23. PMID:19000823[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

  1. ↑ Wu YH, Ko TP, Guo RT, Hu SM, Chuang LM, Wang AH. Structural basis for catalytic and inhibitory mechanisms of human prostaglandin reductase PTGR2. Structure. 2008 Nov 12;16(11):1714-23. PMID:19000823 doi:10.1016/j.str.2008.09.007

2zb8, resolution 2.00Å

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OCA
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