2hfk

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[[Image:2hfk.gif|left|200px]]
[[Image:2hfk.gif|left|200px]]
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{{Structure
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<!--
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|PDB= 2hfk |SIZE=350|CAPTION= <scene name='initialview01'>2hfk</scene>, resolution 1.79&Aring;
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The line below this paragraph, containing "STRUCTURE_2hfk", creates the "Structure Box" on the page.
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|SITE=
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You may change the PDB parameter (which sets the PDB file loaded into the applet)
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|LIGAND= <scene name='pdbligand=DMS:DIMETHYL+SULFOXIDE'>DMS</scene>, <scene name='pdbligand=E4H:(3R,4S,5S,7R,9E,11R,12R)-12-ETHYL-4-HYDROXY-3,5,7,11-TETRAMETHYLOXACYCLODODEC-9-ENE-2,8-DIONE'>E4H</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>
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or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
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|ACTIVITY=
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or leave the SCENE parameter empty for the default display.
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|GENE= pikAIV ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=54571 Streptomyces venezuelae])
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-->
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|DOMAIN=
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{{STRUCTURE_2hfk| PDB=2hfk | SCENE= }}
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|RELATEDENTRY=[[1mna|1MNA]], [[2hfj|2HFJ]]
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|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2hfk FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2hfk OCA], [http://www.ebi.ac.uk/pdbsum/2hfk PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=2hfk RCSB]</span>
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}}
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'''Pikromycin thioesterase in complex with product 10-deoxymethynolide'''
'''Pikromycin thioesterase in complex with product 10-deoxymethynolide'''
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[[Category: Sherman, D H.]]
[[Category: Sherman, D H.]]
[[Category: Smith, J L.]]
[[Category: Smith, J L.]]
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[[Category: alpha/beta hydrolase]]
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[[Category: Alpha/beta hydrolase]]
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[[Category: thioesterase]]
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[[Category: Thioesterase]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May 4 06:13:56 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 03:29:39 2008''
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Revision as of 03:13, 4 May 2008

Template:STRUCTURE 2hfk

Pikromycin thioesterase in complex with product 10-deoxymethynolide


Overview

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

2HFK is a Single protein structure of sequence from Streptomyces venezuelae. Full crystallographic information is available from OCA.

Reference

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 Page seeded by OCA on Sun May 4 06:13:56 2008

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