This old version of Proteopedia is provided for student assignments while the new version is undergoing repairs. Content and edits done in this old version of Proteopedia after March 1, 2026 will eventually be lost when it is retired in about June of 2026.

Apply for new accounts at the new Proteopedia. Your logins will work in both the old and new versions.


1pgf

From Proteopedia

(Difference between revisions)
Jump to: navigation, search
Current revision (05:55, 17 April 2024) (edit) (undo)
 
(17 intermediate revisions not shown.)
Line 1: Line 1:
-
[[Image:1pgf.gif|left|200px]]<br /><applet load="1pgf" size="450" color="white" frame="true" align="right" spinBox="true"
 
-
caption="1pgf, resolution 4.5&Aring;" />
 
-
'''PROSTAGLANDIN H2 SYNTHASE-1 COMPLEXED WITH 1-(4-IODOBENZOYL)-5-METHOXY-2-METHYLINDOLE-3-ACETIC ACID (IODOINDOMETHACIN), CIS MODEL'''<br />
 
-
==Overview==
+
==PROSTAGLANDIN H2 SYNTHASE-1 COMPLEXED WITH 1-(4-IODOBENZOYL)-5-METHOXY-2-METHYLINDOLE-3-ACETIC ACID (IODOINDOMETHACIN), CIS MODEL==
-
The cyclooxygenase activity of the membrane protein prostaglandin H2, synthase isoform 1 (PGHS-1) is the target of the nonsteroidal, antiinflammatory drugs (NSAIDs). The X-ray crystal structures of PGHS-1 in, complex with the NSAIDs flurbiprofen and bromoaspirin have been determined, previously [Picot, D., et al. (1994) Nature 367, 243-249; Loll, P. J., et, al. (1995) Nat. Struct. Biol. 2, 637-643]. We report here the preparation, and characterization of novel potent iodinated analogs of the NSAIDs, indomethacin and suprofen, as well as the refined X-ray crystal structures, of their complexes with PGHS-1. The PGHS-iodosuprofen complex structure, has been refined at 3.5 A to an R-value of 0.189 and shows the suprofen, analog to share a common mode of binding with flurbiprofen. The, PGHS-iodoindomethacin complex structure has been refined at 4.5 A to an, R-value of 0.254. The low resolution of the iodoindomethacin complex, structure precludes detailed modeling of drug-enzyme interactions, but the, electron-dense iodine atom of the inhibitor has been unambiguously, located, allowing for the placement and approximate orientation of the, inhibitor in the enzyme's active site. We have modeled two equally likely, binding modes for iodoindomethacin, corresponding to the two principal, conformers of the inhibitor. Like flurbiprofen, iodosuprofen and, iodoindomethacin bind at the end of the long channel which leads into the, enzyme active site. Binding at this site presumably blocks access of, substrate to Tyr-385, a residue essential for catalysis. No evidence is, seen for significant protein conformational differences between the, iodoindomethacin and iodosuprofen of flurbiprofen complex structures.
+
<StructureSection load='1pgf' size='340' side='right'caption='[[1pgf]], [[Resolution|resolution]] 4.50&Aring;' scene=''>
 +
== Structural highlights ==
 +
<table><tr><td colspan='2'>[[1pgf]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Ovis_aries Ovis aries]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1PGF OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1PGF FirstGlance]. <br>
 +
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 4.5&#8491;</td></tr>
 +
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=HEM:PROTOPORPHYRIN+IX+CONTAINING+FE'>HEM</scene>, <scene name='pdbligand=IMM:1-(4-IODOBENZOYL)-5-METHOXY-2-METHYL+INDOLE-3-ACETIC+ACID'>IMM</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</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=1pgf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1pgf OCA], [https://pdbe.org/1pgf PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1pgf RCSB], [https://www.ebi.ac.uk/pdbsum/1pgf PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1pgf ProSAT]</span></td></tr>
 +
</table>
 +
== Function ==
 +
[https://www.uniprot.org/uniprot/PGH1_SHEEP PGH1_SHEEP] May play an important role in regulating or promoting cell proliferation in some normal and neoplastically transformed cells.
 +
== 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/pg/1pgf_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=1pgf ConSurf].
 +
<div style="clear:both"></div>
-
==About this Structure==
+
==See Also==
-
1PGF is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Ovis_aries Ovis aries] with NAG, HEM and IMM as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Prostaglandin-endoperoxide_synthase Prostaglandin-endoperoxide synthase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.14.99.1 1.14.99.1] Known structural/functional Sites: <scene name='pdbsite=COB:The Cyclooxygenase Active Site Is Located Within A Long ...'>COB</scene>, <scene name='pdbsite=COX:The Cyclooxygenase Active Site Is Located Within A Long ...'>COX</scene>, <scene name='pdbsite=PEB:The Peroxidase Active Site Is At The Heme (Hem 601) Site ...'>PEB</scene> and <scene name='pdbsite=PER:The Peroxidase Active Site Is At The Heme (Hem 601) Site ...'>PER</scene>. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1PGF OCA].
+
*[[Cyclooxygenase 3D structures|Cyclooxygenase 3D structures]]
-
 
+
__TOC__
-
==Reference==
+
</StructureSection>
-
Synthesis and use of iodinated nonsteroidal antiinflammatory drug analogs as crystallographic probes of the prostaglandin H2 synthase cyclooxygenase active site., Loll PJ, Picot D, Ekabo O, Garavito RM, Biochemistry. 1996 Jun 11;35(23):7330-40. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=8652509 8652509]
+
[[Category: Large Structures]]
[[Category: Ovis aries]]
[[Category: Ovis aries]]
-
[[Category: Prostaglandin-endoperoxide synthase]]
+
[[Category: Garavito RM]]
-
[[Category: Single protein]]
+
[[Category: Loll PJ]]
-
[[Category: Garavito, R.M.]]
+
[[Category: Picot D]]
-
[[Category: Loll, P.J.]]
+
-
[[Category: Picot, D.]]
+
-
[[Category: HEM]]
+
-
[[Category: IMM]]
+
-
[[Category: NAG]]
+
-
[[Category: dioxygenase]]
+
-
[[Category: oxidoreductase]]
+
-
[[Category: peroxidase]]
+
-
 
+
-
''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Tue Dec 18 17:51:30 2007''
+

Current revision

PROSTAGLANDIN H2 SYNTHASE-1 COMPLEXED WITH 1-(4-IODOBENZOYL)-5-METHOXY-2-METHYLINDOLE-3-ACETIC ACID (IODOINDOMETHACIN), CIS MODEL

PDB ID 1pgf

Drag the structure with the mouse to rotate

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/1pgf"
Personal tools