1rm0: Difference between revisions

Revision as of 15:52, 21 February 2008

Crystal Structure of Myo-Inositol 1-Phosphate Synthase From Saccharomyces cerevisiae In Complex With NAD+ and 2-deoxy-D-glucitol 6-(E)-vinylhomophosphonate

OverviewOverview

1l-myo-inositol 1-phosphate (MIP) synthase catalyzes the conversion of d-glucose 6-phosphate to 1l-myo-inositol 1-phosphate, the first and rate-limiting step in the biosynthesis of all inositol-containing compounds. It involves an oxidation, enolization, intramolecular aldol cyclization, and reduction. Here we present the structure of MIP synthase in complex with NAD(+) and a high-affinity inhibitor, 2-deoxy-d-glucitol 6-(E)-vinylhomophosphonate. This structure reveals interactions between the enzyme active site residues and the inhibitor that are significantly different from that proposed for 2-deoxy-d-glucitol 6-phosphate in the previously published structure of MIP synthase-NAD(+)-2-deoxy-d-glucitol 6-phosphate. There are several other conformational changes in NAD(+) and the enzyme active site as well. Based on the new structural data, we propose a new and completely different mechanism for MIP synthase.

About this StructureAbout this Structure

1RM0 is a Single protein structure of sequence from Saccharomyces cerevisiae with , and as ligands. Active as Inositol-3-phosphate synthase, with EC number 5.5.1.4 Full crystallographic information is available from OCA.

ReferenceReference

The structure of the 1L-myo-inositol-1-phosphate synthase-NAD+-2-deoxy-D-glucitol 6-(E)-vinylhomophosphonate complex demands a revision of the enzyme mechanism., Jin X, Foley KM, Geiger JH, J Biol Chem. 2004 Apr 2;279(14):13889-95. Epub 2003 Dec 18. PMID:14684747

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-[[Image:1rm0.gif|left|200px]]<br /><applet load="1rm0" size="450" color="white" frame="true" align="right" spinBox="true"
+[[Image:1rm0.gif|left|200px]]<br /><applet load="1rm0" size="350" color="white" frame="true" align="right" spinBox="true"
 caption="1rm0, resolution 2.05&Aring;" />
 '''Crystal Structure of Myo-Inositol 1-Phosphate Synthase From Saccharomyces cerevisiae In Complex With NAD+ and 2-deoxy-D-glucitol 6-(E)-vinylhomophosphonate'''<br />
 ==Overview==
-l-myo-inositol 1-phosphate (MIP) synthase catalyzes the conversion of, d-glucose 6-phosphate to 1l-myo-inositol 1-phosphate, the first and, rate-limiting step in the biosynthesis of all inositol-containing, compounds. It involves an oxidation, enolization, intramolecular aldol, cyclization, and reduction. Here we present the structure of MIP synthase, in complex with NAD(+) and a high-affinity inhibitor, 2-deoxy-d-glucitol, 6-(E)-vinylhomophosphonate. This structure reveals interactions between, the enzyme active site residues and the inhibitor that are significantly, different from that proposed for 2-deoxy-d-glucitol 6-phosphate in the, previously published structure of MIP synthase-NAD(+)-2-deoxy-d-glucitol, 6-phosphate. There are several other conformational changes in NAD(+) and, the enzyme active site as well. Based on the new structural data, we, propose a new and completely different mechanism for MIP synthase.
+l-myo-inositol 1-phosphate (MIP) synthase catalyzes the conversion of d-glucose 6-phosphate to 1l-myo-inositol 1-phosphate, the first and rate-limiting step in the biosynthesis of all inositol-containing compounds. It involves an oxidation, enolization, intramolecular aldol cyclization, and reduction. Here we present the structure of MIP synthase in complex with NAD(+) and a high-affinity inhibitor, 2-deoxy-d-glucitol 6-(E)-vinylhomophosphonate. This structure reveals interactions between the enzyme active site residues and the inhibitor that are significantly different from that proposed for 2-deoxy-d-glucitol 6-phosphate in the previously published structure of MIP synthase-NAD(+)-2-deoxy-d-glucitol 6-phosphate. There are several other conformational changes in NAD(+) and the enzyme active site as well. Based on the new structural data, we propose a new and completely different mechanism for MIP synthase.
 ==About this Structure==
-RM0 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Saccharomyces_cerevisiae Saccharomyces cerevisiae] with MN, D6P and NAI as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Inositol-3-phosphate_synthase Inositol-3-phosphate synthase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=5.5.1.4 5.5.1.4] Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1RM0 OCA].
+RM0 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Saccharomyces_cerevisiae Saccharomyces cerevisiae] with <scene name='pdbligand=MN:'>MN</scene>, <scene name='pdbligand=D6P:'>D6P</scene> and <scene name='pdbligand=NAI:'>NAI</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Inositol-3-phosphate_synthase Inositol-3-phosphate synthase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=5.5.1.4 5.5.1.4] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1RM0 OCA].
 ==Reference==
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 [[Category: Saccharomyces cerevisiae]]
 [[Category: Single protein]]
-[[Category: Foley, K.M.]]
+[[Category: Foley, K M.]]
-[[Category: Geiger, J.H.]]
+[[Category: Geiger, J H.]]
 [[Category: Jin, X.]]
 [[Category: D6P]]
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 [[Category: myo-inositol 1-phosphate synthase]]
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