1w3v: Difference between revisions

Revision as of 13:07, 3 May 2008

ISOPENICILLIN N SYNTHASE D-(L-A-AMINOADIPOYL)-(3R)-METHYL-L-CYSTEINE D-A-HYDROXYISOVALERYL ESTER COMPLEX (ANAEROBIC)

OverviewOverview

Isopenicillin N synthase (IPNS) is a non-heme iron(ii)-dependent oxidase that is central to penicillin biosynthesis. Herein, we report mechanistic studies of the IPNS reaction in the crystalline state, using the substrate analogue delta-(L-alpha-aminoadipoyl)-(3R)-methyl-L-cysteine D-alpha-hydroxyisovaleryl ester (AmCOV) to probe the early stages of the catalytic cycle. The X-ray crystal structure of the anaerobic IPNS:Fe(II):AmCOV complex was solved to 1.40 A resolution, and it reveals several subtle differences in the active site relative to the complex of the enzyme with its natural substrate. The crystalline IPNS:Fe(II):AmCOV complex was then exposed to oxygen gas at high pressure; this brought about reaction to give what appears to be a hydroxymethyl/ene-thiol product. A mechanism for this reaction is proposed. These results offer further insight into the delicate interplay of steric and electronic effects in the IPNS active site and the mechanistic intricacies of this remarkable enzyme.

About this StructureAbout this Structure

1W3V is a Single protein structure of sequence from Emericella nidulans. Full crystallographic information is available from OCA.

ReferenceReference

Unexpected oxidation of a depsipeptide substrate analogue in crystalline isopenicillin N synthase., Daruzzaman A, Clifton IJ, Adlington RM, Baldwin JE, Rutledge PJ, Chembiochem. 2006 Feb;7(2):351-8. PMID:16444759 Page seeded by OCA on Sat May 3 13:07:18 2008

Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

OCA

@@ Line 1: / Line 1: @@
 [[Image:1w3v.gif|left|200px]]
- {{Structure
+<!--
-|PDB= 1w3v |SIZE=350|CAPTION= <scene name='initialview01'>1w3v</scene>, resolution 1.40&Aring;
+The line below this paragraph, containing "STRUCTURE_1w3v", creates the "Structure Box" on the page.
-|SITE= <scene name='pdbsite=AC1:Mdz+Binding+Site+For+Chain+A'>AC1</scene>
+You may change the PDB parameter (which sets the PDB file loaded into the applet)
-|LIGAND= <scene name='pdbligand=FE2:FE+(II)+ION'>FE2</scene>, <scene name='pdbligand=MDZ:N~6~-METHYL-6-OXO-L-LYSINE+-+2-[(3-MERCAPTOBUTANOYL)OXY]-3-METHYLBUTANOIC+ACID'>MDZ</scene>
+or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
-|ACTIVITY= <span class='plainlinks'>[http://en.wikipedia.org/wiki/Isopenicillin-N_synthase Isopenicillin-N synthase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.21.3.1 1.21.3.1] </span>
+or leave the SCENE parameter empty for the default display.
-|GENE=
+-->
-|DOMAIN=
+{{STRUCTURE_1w3v|  PDB=1w3v  |  SCENE=  }}
-|RELATEDENTRY=
-|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1w3v FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1w3v OCA], [http://www.ebi.ac.uk/pdbsum/1w3v PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1w3v RCSB]</span>
-}}
 '''ISOPENICILLIN N SYNTHASE D-(L-A-AMINOADIPOYL)-(3R)-METHYL-L-CYSTEINE D-A-HYDROXYISOVALERYL ESTER COMPLEX (ANAEROBIC)'''
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 [[Category: Rutledge, P J.]]
 [[Category: 3d-structure]]
-[[Category: antibiotic biosynthesis]]
+[[Category: Antibiotic biosynthesis]]
-[[Category: b-lactam antibiotic]]
+[[Category: B-lactam antibiotic]]
-[[Category: iron]]
+[[Category: Iron]]
-[[Category: oxidoreductase]]
+[[Category: Oxidoreductase]]
-[[Category: oxygenase]]
+[[Category: Oxygenase]]
-[[Category: penicillin biosynthesis]]
+[[Category: Penicillin biosynthesis]]
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May  3 13:07:18 2008''
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 00:30:51 2008''