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2f38

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Revision as of 08:36, 14 June 2018

Crystal structure of prostaglandin F synathase containing bimatoprost

Structural highlights

2f38 is a 1 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	,
Gene:	AKR1C3, DDH1, KIAA0119, PGFS (HUMAN)
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[AK1C3_HUMAN] Catalyzes the conversion of aldehydes and ketones to alcohols. Catalyzes the reduction of prostaglandin (PG) D2, PGH2 and phenanthrenequinone (PQ) and the oxidation of 9-alpha,11-beta-PGF2 to PGD2. Functions as a bi-directional 3-alpha-, 17-beta- and 20-alpha HSD. Can interconvert active androgens, estrogens and progestins with their cognate inactive metabolites. Preferentially transforms androstenedione (4-dione) to testosterone.

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

Prostaglandin H(2) (PGH(2)) formed from arachidonic acid is an unstable intermediate and is efficiently converted into more stable arachidonate metabolites by the action of enzymes. Prostaglandin F synthase (PGFS) has dual catalytic activities: formation of PGF(2)(alpha) from PGH(2) by the PGH(2) 9,11-endoperoxide reductase activity and 9alpha,11beta-PGF(2) (PGF(2)(alphabeta)) from PGD(2) by the PGD(2) 11-ketoreductase activity in the presence of NADPH. Bimatoprost (BMP), which is a highly effective ocular hypotensive agent, is a PGF(2)(alpha) analogue that inhibits both the PGD(2) 11-ketoreductase and PGH(2) 9,11-endoperoxide reductase activities of PGFS. To examine the catalytic mechanism of PGH(2) 9,11-endoperoxide reductase, a crystal structure of PGFS[NADPH + BMP] has been determined at 2.0 A resolution. BMP binds near the PGD(2) binding site, but the alpha- and omega-chains of BMP are locate on the omega- and alpha-chains of PGD(2), respectively. Consequently, the bound BMP and PGD(2) direct their opposite faces of the cyclopentane moieties toward the nicotinamide ring of the bound NADP. The alpha- and omega-chains of BMP are involved in H-bonding with protein residues, while the cyclopentane moiety is surrounded by water molecules and is not directly attached to either the protein or the bound NADPH, indicating that the cyclopentane moiety is movable in the active site. From the complex structure, two model structures of PGFS containing PGF(2)(alpha) and PGH(2) were built. On the basis of the model structures and inhibition data, a putative catalytic mechanism of PGH(2) 9,11-endoperoxide reductase of PGFS is proposed. Formation of PGF(2)(alpha) from PGH(2) most likely involves a direct hydride transfer from the bound NADPH to the endoperoxide of PGH(2) without the participation of specific amino acid residues.

Prostaglandin F2alpha formation from prostaglandin H2 by prostaglandin F synthase (PGFS): crystal structure of PGFS containing bimatoprost.,Komoto J, Yamada T, Watanabe K, Woodward DF, Takusagawa F Biochemistry. 2006 Feb 21;45(7):1987-96. PMID:16475787^[1]

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

References

↑ Komoto J, Yamada T, Watanabe K, Woodward DF, Takusagawa F. Prostaglandin F2alpha formation from prostaglandin H2 by prostaglandin F synthase (PGFS): crystal structure of PGFS containing bimatoprost. Biochemistry. 2006 Feb 21;45(7):1987-96. PMID:16475787 doi:10.1021/bi051861t

1 Structural highlights
2 Function
3 Evolutionary Conservation
4 Publication Abstract from PubMed
5 See Also
6 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/2f38"

@@ Line 1: / Line 1: @@
 ==Crystal structure of prostaglandin F synathase containing bimatoprost==
 <StructureSection load='2f38' size='340' side='right' caption='[[2f38]], [[Resolution|resolution]] 2.00&Aring;' scene=''>
@@ Line 5: / Line 6: @@
 </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=15M:(5Z)-7-{(1R,2R,3R,5S)-3,5-DIHYDROXY-2-[(1E,3S)-3-HYDROXY-5-PHENYLPENT-1-ENYL]CYCLOPENTYL}-N-ETHYLHEPT-5-ENAMIDE'>15M</scene>, <scene name='pdbligand=NAP:NADP+NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NAP</scene></td></tr>
 <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">AKR1C3, DDH1, KIAA0119, PGFS ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
-<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2f38 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2f38 OCA], [http://pdbe.org/2f38 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2f38 RCSB], [http://www.ebi.ac.uk/pdbsum/2f38 PDBsum]</span></td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2f38 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2f38 OCA], [http://pdbe.org/2f38 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2f38 RCSB], [http://www.ebi.ac.uk/pdbsum/2f38 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2f38 ProSAT]</span></td></tr>
 </table>
 == Function ==
@@ Line 13: / Line 14: @@
 Check<jmol>
   <jmolCheckbox>
-    <scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/f3/2f38_consurf.spt"</scriptWhenChecked>
+    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/f3/2f38_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].
+</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=2f38 ConSurf].
 <div style="clear:both"></div>
 <div style="background-color:#fffaf0;">

2f38

From Proteopedia

Revision as of 08:36, 14 June 2018

Crystal structure of prostaglandin F synathase containing bimatoprost

Structural highlights

Function

Evolutionary Conservation

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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