'''ISOPENICILLIN N SYNTHASE AMINOADIPOYL-CYSTEINYL-GLYCINE-FE-NO COMPLEX'''
===ISOPENICILLIN N SYNTHASE AMINOADIPOYL-CYSTEINYL-GLYCINE-FE-NO COMPLEX===
==Overview==
<!--
Isopenicillin N synthase (IPNS), a non-heme iron(II)-dependent oxidase, catalyzes conversion of the tripeptide delta-(l-alpha-aminoadipoyl)-l-cysteinyl-d-valine (ACV) to bicyclic isopenicillin N (IPN), concomitant with the reduction of dioxygen to two molecules of water. Incubation of the "truncated"substrate analogues delta-(l-alpha-aminoadipoyl)-l-cysteinyl-glycine (ACG) and delta-(l-alpha-aminoadipoyl)-l-cysteinyl-d-alanine (ACA) with IPNS has previously been shown to afford acyclic products, in which the substrate cysteinyl residue has undergone a two-electron oxidation. We report X-ray crystal structures for the anaerobic IPNS/Fe(II)/ACG and IPNS/Fe(II)/ACA complexes, both in the absence and presence of the dioxygen analogue nitric oxide. The overall protein structures are very similar to those of the corresponding IPNS/Fe(II)/ACV complexes; however, significant differences are apparent in the vicinity of the active site iron. The structure of the IPNS/Fe(II)/ACG complex reveals that the C-terminal carboxylate of this substrate is oriented toward the active site iron atom, apparently hydrogen-bonded to an additional water ligand at the metal; this is a different binding mode to that observed in the IPNS/Fe(II)/ACV complex. ACA binds to the metal in a manner that is intermediate between those observed for ACV and ACG. The addition of NO to these complexes initiates conformational changes such that both the IPNS/Fe(II)/ACG/NO and IPNS/Fe(II)/ACA/NO structures closely resemble the IPNS/Fe(II)/ACV/NO complex. These results further demonstrate the feasibility of metal-centered rearrangements in catalysis by non-heme iron enzymes and provide insight into the delicate balance between hydrophilic-hydrophobic interactions and steric effects in the IPNS active site.
The line below this paragraph, {{ABSTRACT_PUBMED_15850395}}, adds the Publication Abstract to the page
(as it appears on PubMed at http://www.pubmed.gov), where 15850395 is the PubMed ID number.
-->
{{ABSTRACT_PUBMED_15850395}}
==About this Structure==
==About this Structure==
Line 30:
Line 34:
[[Category: Oxygenase]]
[[Category: Oxygenase]]
[[Category: Penicillin biosynthesis]]
[[Category: Penicillin biosynthesis]]
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 12:58:36 2008''
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Jul 28 17:10:28 2008''
Revision as of 17:10, 28 July 2008
This article has been automatically seeded. Changes to this page should pertain to the PDB entry only and not to the protein or biomolecule in general.
Structural studies on the reaction of isopenicillin N synthase with the truncated substrate analogues delta-(L-alpha-aminoadipoyl)-L-cysteinyl-glycine and delta-(L-alpha-aminoadipoyl)-L-cysteinyl-D-alanine., Long AJ, Clifton IJ, Roach PL, Baldwin JE, Rutledge PJ, Schofield CJ, Biochemistry. 2005 May 3;44(17):6619-28. PMID:15850395
