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.


2hfj

From Proteopedia

(Difference between revisions)
Jump to: navigation, search
(New page: 200px<br /><applet load="2hfj" size="350" color="white" frame="true" align="right" spinBox="true" caption="2hfj, resolution 1.95&Aring;" /> '''Pikromycin thioester...)
Current revision (07:39, 17 March 2021) (edit) (undo)
 
(13 intermediate revisions not shown.)
Line 1: Line 1:
-
[[Image:2hfj.gif|left|200px]]<br /><applet load="2hfj" size="350" color="white" frame="true" align="right" spinBox="true"
 
-
caption="2hfj, resolution 1.95&Aring;" />
 
-
'''Pikromycin thioesterase with covalent pentaketide affinity label'''<br />
 
-
==Overview==
+
==Pikromycin thioesterase with covalent pentaketide affinity label==
-
Polyketides are a class of biologically active microbial and plant-derived, metabolites that possess a high degree of structural and functional, diversity and include many human therapeutics, among them anti-infective, and anti-cancer drugs, growth promoters and anti-parasitic agents. The, macrolide antibiotics, characterized by a glycoside-linked macrolactone, constitute an important class of polyketides, including erythromycin and, the natural ketolide anti-infective agent pikromycin. Here we describe new, mechanistic details of macrolactone ring formation catalyzed by the, pikromycin polyketide synthase thioesterase domain from Streptomyces, venezuelae. A pentaketide phosphonate mimic of the final pikromycin linear, chain-elongation intermediate was synthesized and shown to be an active, site affinity label. The crystal structures of the affinity-labeled enzyme, and of a 12-membered-ring macrolactone product complex suggest a mechanism, for cyclization in which a hydrophilic barrier in the enzyme and, structural restraints of the substrate induce a curled conformation to, direct macrolactone ring formation.
+
<StructureSection load='2hfj' size='340' side='right'caption='[[2hfj]], [[Resolution|resolution]] 1.95&Aring;' scene=''>
 +
== Structural highlights ==
 +
<table><tr><td colspan='2'>[[2hfj]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/As_4.1526 As 4.1526]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2HFJ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2HFJ FirstGlance]. <br>
 +
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=DMS:DIMETHYL+SULFOXIDE'>DMS</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=YML:[(3R,4S,5S,7R)-4,8-DIHYDROXY-3,5,7-TRIMETHYL-2-OXOOCTYL]PHOSPHONIC+ACID'>YML</scene></td></tr>
 +
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[1mna|1mna]], [[2hfk|2hfk]]</div></td></tr>
 +
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">pikAIV ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=54571 AS 4.1526])</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=2hfj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2hfj OCA], [https://pdbe.org/2hfj PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2hfj RCSB], [https://www.ebi.ac.uk/pdbsum/2hfj PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2hfj ProSAT]</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/hf/2hfj_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=2hfj ConSurf].
 +
<div style="clear:both"></div>
 +
<div style="background-color:#fffaf0;">
 +
== Publication Abstract from PubMed ==
 +
Polyketides are a class of biologically active microbial and plant-derived metabolites that possess a high degree of structural and functional diversity and include many human therapeutics, among them anti-infective and anti-cancer drugs, growth promoters and anti-parasitic agents. The macrolide antibiotics, characterized by a glycoside-linked macrolactone, constitute an important class of polyketides, including erythromycin and the natural ketolide anti-infective agent pikromycin. Here we describe new mechanistic details of macrolactone ring formation catalyzed by the pikromycin polyketide synthase thioesterase domain from Streptomyces venezuelae. A pentaketide phosphonate mimic of the final pikromycin linear chain-elongation intermediate was synthesized and shown to be an active site affinity label. The crystal structures of the affinity-labeled enzyme and of a 12-membered-ring macrolactone product complex suggest a mechanism for cyclization in which a hydrophilic barrier in the enzyme and structural restraints of the substrate induce a curled conformation to direct macrolactone ring formation.
-
==About this Structure==
+
Structural basis for macrolactonization by the pikromycin thioesterase.,Akey DL, Kittendorf JD, Giraldes JW, Fecik RA, Sherman DH, Smith JL Nat Chem Biol. 2006 Oct;2(10):537-42. Epub 2006 Sep 10. PMID:16969372<ref>PMID:16969372</ref>
-
2HFJ is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Streptomyces_venezuelae Streptomyces venezuelae] with <scene name='pdbligand=SO4:'>SO4</scene>, <scene name='pdbligand=MG:'>MG</scene>, <scene name='pdbligand=DMS:'>DMS</scene> and <scene name='pdbligand=YML:'>YML</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2HFJ OCA].
+
-
==Reference==
+
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-
Structural basis for macrolactonization by the pikromycin thioesterase., Akey DL, Kittendorf JD, Giraldes JW, Fecik RA, Sherman DH, Smith JL, Nat Chem Biol. 2006 Oct;2(10):537-42. Epub 2006 Sep 10. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=16969372 16969372]
+
</div>
-
[[Category: Single protein]]
+
<div class="pdbe-citations 2hfj" style="background-color:#fffaf0;"></div>
-
[[Category: Streptomyces venezuelae]]
+
== References ==
-
[[Category: Akey, D.L.]]
+
<references/>
-
[[Category: Fecik, R.A.]]
+
__TOC__
-
[[Category: Giraldes, J.W.]]
+
</StructureSection>
-
[[Category: Kittendorf, J.D.]]
+
[[Category: As 4 1526]]
-
[[Category: Sherman, D.H.]]
+
[[Category: Large Structures]]
-
[[Category: Smith, J.L.]]
+
[[Category: Akey, D L]]
-
[[Category: DMS]]
+
[[Category: Fecik, R A]]
-
[[Category: MG]]
+
[[Category: Giraldes, J W]]
-
[[Category: SO4]]
+
[[Category: Kittendorf, J D]]
-
[[Category: YML]]
+
[[Category: Sherman, D H]]
-
[[Category: alpha/beta hydrolase]]
+
[[Category: Smith, J L]]
-
[[Category: thioesterase]]
+
[[Category: Alpha/beta hydrolase]]
-
 
+
[[Category: Hydrolase]]
-
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Tue Jan 29 20:20:00 2008''
+
[[Category: Thioesterase]]

Current revision

Pikromycin thioesterase with covalent pentaketide affinity label

PDB ID 2hfj

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/2hfj"
Personal tools