1dcs: Difference between revisions

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[[Image:1dcs.gif|left|200px]]<br /><applet load="1dcs" size="~~450~~" color="white" frame="true" align="right" spinBox="true"

[[Image:1dcs.gif|left|200px]]<br /><applet load="1dcs" size="350" color="white" frame="true" align="right" spinBox="true"

caption="1dcs, resolution 1.3Å" />

'''DEACETOXYCEPHALOSPORIN C SYNTHASE FROM S. CLAVULIGERUS'''<br />

==Overview==

Penicillins and cephalosporins are among the most widely used therapeutic, agents. These antibiotics are produced from fermentation-derived materials, as their chemical synthesis is not commercially viable. Unconventional, steps in their biosynthesis are catalysed by Fe(II)-dependent, oxidases/oxygenases; isopenicillin N synthase (IPNS) creates in one step, the bicyclic nucleus of penicillins, and deacetoxycephalosporin C synthase, (DAOCS) catalyses the expansion of the penicillin nucleus into the nucleus, of cephalosporins. Both enzymes use dioxygen-derived ferryl intermediates, in catalysis but, in contrast to IPNS, the ferryl form of DAOCS is, produced by the oxidative splitting of a co-substrate, 2-oxoglutarate, (alpha-ketoglutarate). This route of controlled ferryl formation and, reaction is common to many mononuclear ferrous enzymes, which participate, in a broader range of reactions than their well-characterized, counterparts, the haem enzymes. Here we report the first crystal structure, of a 2-oxoacid-dependent oxygenase. High-resolution structures for, apo-DAOCS, the enzyme complexed with Fe(II), and with Fe(II) and, 2-oxoglutarate, were obtained from merohedrally twinned crystals. Using a, model based on these structures, we propose a mechanism for ferryl, formation.

Penicillins and cephalosporins are among the most widely used therapeutic agents. These antibiotics are produced from fermentation-derived materials as their chemical synthesis is not commercially viable. Unconventional steps in their biosynthesis are catalysed by Fe(II)-dependent oxidases/oxygenases; isopenicillin N synthase (IPNS) creates in one step the bicyclic nucleus of penicillins, and deacetoxycephalosporin C synthase (DAOCS) catalyses the expansion of the penicillin nucleus into the nucleus of cephalosporins. Both enzymes use dioxygen-derived ferryl intermediates in catalysis but, in contrast to IPNS, the ferryl form of DAOCS is produced by the oxidative splitting of a co-substrate, 2-oxoglutarate (alpha-ketoglutarate). This route of controlled ferryl formation and reaction is common to many mononuclear ferrous enzymes, which participate in a broader range of reactions than their well-characterized counterparts, the haem enzymes. Here we report the first crystal structure of a 2-oxoacid-dependent oxygenase. High-resolution structures for apo-DAOCS, the enzyme complexed with Fe(II), and with Fe(II) and 2-oxoglutarate, were obtained from merohedrally twinned crystals. Using a model based on these structures, we propose a mechanism for ferryl formation.

==About this Structure==

1DCS is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Streptomyces_clavuligerus Streptomyces clavuligerus] with SO4 as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http://~~ispc~~.weizmann.ac.il/oca-bin/ocashort?id=1DCS OCA].

1DCS is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Streptomyces_clavuligerus Streptomyces clavuligerus] with <scene name='pdbligand=SO4:'>SO4</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1DCS OCA].

==Reference==

Line 14:

[[Category: Streptomyces clavuligerus]]

[[Category: Andersson, I.]]

[[Category: Baldwin, J.E.]]

[[Category: Baldwin, J E.]]

[[Category: Hajdu, J.]]

[[Category: Hara, T.]]

[[Category: Lee, H.J.]]

[[Category: Lee, H J.]]

[[Category: Lloyd, M.D.]]

[[Category: Lloyd, M D.]]

[[Category: Perrakis, A.]]

[[Category: Ramaswamy, S.]]

[[Category: Scheltinga, A.C.Terwisscha.Van.]]

[[Category: Scheltinga, A C.Terwisscha Van.]]

[[Category: Schofield, C.J.]]

[[Category: Schofield, C J.]]

[[Category: Thompson, A.]]

[[Category: Valegard, K.]]

Line 34:

[[Category: oxidoreductase]]

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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 12:15:22 2008''

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@@ Line 1: / Line 1: @@
-[[Image:1dcs.gif|left|200px]]<br /><applet load="1dcs" size="450" color="white" frame="true" align="right" spinBox="true"
+[[Image:1dcs.gif|left|200px]]<br /><applet load="1dcs" size="350" color="white" frame="true" align="right" spinBox="true"
 caption="1dcs, resolution 1.3&Aring;" />
 '''DEACETOXYCEPHALOSPORIN C SYNTHASE FROM S. CLAVULIGERUS'''<br />
 ==Overview==
-Penicillins and cephalosporins are among the most widely used therapeutic, agents. These antibiotics are produced from fermentation-derived materials, as their chemical synthesis is not commercially viable. Unconventional, steps in their biosynthesis are catalysed by Fe(II)-dependent, oxidases/oxygenases; isopenicillin N synthase (IPNS) creates in one step, the bicyclic nucleus of penicillins, and deacetoxycephalosporin C synthase, (DAOCS) catalyses the expansion of the penicillin nucleus into the nucleus, of cephalosporins. Both enzymes use dioxygen-derived ferryl intermediates, in catalysis but, in contrast to IPNS, the ferryl form of DAOCS is, produced by the oxidative splitting of a co-substrate, 2-oxoglutarate, (alpha-ketoglutarate). This route of controlled ferryl formation and, reaction is common to many mononuclear ferrous enzymes, which participate, in a broader range of reactions than their well-characterized, counterparts, the haem enzymes. Here we report the first crystal structure, of a 2-oxoacid-dependent oxygenase. High-resolution structures for, apo-DAOCS, the enzyme complexed with Fe(II), and with Fe(II) and, 2-oxoglutarate, were obtained from merohedrally twinned crystals. Using a, model based on these structures, we propose a mechanism for ferryl, formation.
+Penicillins and cephalosporins are among the most widely used therapeutic agents. These antibiotics are produced from fermentation-derived materials as their chemical synthesis is not commercially viable. Unconventional steps in their biosynthesis are catalysed by Fe(II)-dependent oxidases/oxygenases; isopenicillin N synthase (IPNS) creates in one step the bicyclic nucleus of penicillins, and deacetoxycephalosporin C synthase (DAOCS) catalyses the expansion of the penicillin nucleus into the nucleus of cephalosporins. Both enzymes use dioxygen-derived ferryl intermediates in catalysis but, in contrast to IPNS, the ferryl form of DAOCS is produced by the oxidative splitting of a co-substrate, 2-oxoglutarate (alpha-ketoglutarate). This route of controlled ferryl formation and reaction is common to many mononuclear ferrous enzymes, which participate in a broader range of reactions than their well-characterized counterparts, the haem enzymes. Here we report the first crystal structure of a 2-oxoacid-dependent oxygenase. High-resolution structures for apo-DAOCS, the enzyme complexed with Fe(II), and with Fe(II) and 2-oxoglutarate, were obtained from merohedrally twinned crystals. Using a model based on these structures, we propose a mechanism for ferryl formation.
 ==About this Structure==
-DCS is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Streptomyces_clavuligerus Streptomyces clavuligerus] with SO4 as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1DCS OCA].
+DCS is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Streptomyces_clavuligerus Streptomyces clavuligerus] with <scene name='pdbligand=SO4:'>SO4</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1DCS OCA].
 ==Reference==
@@ Line 14: / Line 14: @@
 [[Category: Streptomyces clavuligerus]]
 [[Category: Andersson, I.]]
-[[Category: Baldwin, J.E.]]
+[[Category: Baldwin, J E.]]
 [[Category: Hajdu, J.]]
 [[Category: Hara, T.]]
-[[Category: Lee, H.J.]]
+[[Category: Lee, H J.]]
-[[Category: Lloyd, M.D.]]
+[[Category: Lloyd, M D.]]
 [[Category: Perrakis, A.]]
 [[Category: Ramaswamy, S.]]
-[[Category: Scheltinga, A.C.Terwisscha.Van.]]
+[[Category: Scheltinga, A C.Terwisscha Van.]]
-[[Category: Schofield, C.J.]]
+[[Category: Schofield, C J.]]
 [[Category: Thompson, A.]]
 [[Category: Valegard, K.]]
@@ Line 34: / Line 34: @@
 [[Category: oxidoreductase]]
-''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Tue Nov 20 13:10:43 2007''
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 12:15:22 2008''