1w3v: Difference between revisions

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==Overview==

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.

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 Structure==

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[[Category: Isopenicillin-N synthase]]

[[Category: Single protein]]

[[Category: Clifton, I.J.]]

[[Category: Clifton, I J.]]

[[Category: Daruzzaman, A.]]

[[Category: Rutledge, P.J.]]

[[Category: Rutledge, P J.]]

[[Category: FE2]]

[[Category: MDZ]]

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[[Category: penicillin biosynthesis]]

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@@ Line 4: / Line 4: @@
 ==Overview==
-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.
+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 Structure==
@@ Line 14: / Line 14: @@
 [[Category: Isopenicillin-N synthase]]
 [[Category: Single protein]]
-[[Category: Clifton, I.J.]]
+[[Category: Clifton, I J.]]
 [[Category: Daruzzaman, A.]]
-[[Category: Rutledge, P.J.]]
+[[Category: Rutledge, P J.]]
 [[Category: FE2]]
 [[Category: MDZ]]
@@ Line 27: / Line 27: @@
 [[Category: penicillin biosynthesis]]
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Feb  3 10:19:03 2008''
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 15:40:09 2008''