1p1h
From Proteopedia
(New page: 200px<br /><applet load="1p1h" size="450" color="white" frame="true" align="right" spinBox="true" caption="1p1h, resolution 1.95Å" /> '''Crystal structure of...) |
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| - | [[Image:1p1h.jpg|left|200px]]<br /><applet load="1p1h" size=" | + | [[Image:1p1h.jpg|left|200px]]<br /><applet load="1p1h" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="1p1h, resolution 1.95Å" /> | caption="1p1h, resolution 1.95Å" /> | ||
'''Crystal structure of the 1L-myo-inositol/NAD+ complex'''<br /> | '''Crystal structure of the 1L-myo-inositol/NAD+ complex'''<br /> | ||
==Overview== | ==Overview== | ||
| - | 1-l-myo-Inositol 1-phosphate synthase catalyzes the conversion of | + | 1-l-myo-Inositol 1-phosphate synthase catalyzes the conversion of d-glucose 6-phosphate to 1-l-myo-inositol 1-phosphate, the first and rate-limiting step in the biosynthesis of all inositol-containing compounds. It involves an oxidation, an intramolecular aldol cyclization and a reduction. Here, the structure of the enzyme in its NAD(+)-bound, NADH-bound and apo forms is presented. These structures confirm that a significant portion of the active site is disordered in the absence of a small molecule, as none of the NAD(+)-bound forms of the enzyme have ordered active sites. On the other hand, the NADH-bound form contains two small molecules in the active site: a phosphate and glycerol. The entire active site is ordered in the presence of these two molecules, completely encapsulating them within the interior cavity. Significant changes in the structure of the active site are also seen, including repositioning of the nicotinamide ring and a motion of a loop region to accommodate the bound phosphate. These changes call into question the mechanism previously proposed for the enzyme. A comparison of the yeast and mycobacterial enzymes shows a surprisingly large change in the relative orientation of the catalytic and Rossmann-fold domains in the two enzymes. |
==About this Structure== | ==About this Structure== | ||
| - | 1P1H 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 NAD as [http://en.wikipedia.org/wiki/ligand ligand]. 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:// | + | 1P1H 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=NAD:'>NAD</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. 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=1P1H OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Saccharomyces cerevisiae]] | [[Category: Saccharomyces cerevisiae]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
| - | [[Category: Geiger, J | + | [[Category: Geiger, J H.]] |
[[Category: Jin, X.]] | [[Category: Jin, X.]] | ||
[[Category: NAD]] | [[Category: NAD]] | ||
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[[Category: nad+]] | [[Category: nad+]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 14:24:03 2008'' |
Revision as of 12:24, 21 February 2008
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Crystal structure of the 1L-myo-inositol/NAD+ complex
Overview
1-l-myo-Inositol 1-phosphate synthase catalyzes the conversion of d-glucose 6-phosphate to 1-l-myo-inositol 1-phosphate, the first and rate-limiting step in the biosynthesis of all inositol-containing compounds. It involves an oxidation, an intramolecular aldol cyclization and a reduction. Here, the structure of the enzyme in its NAD(+)-bound, NADH-bound and apo forms is presented. These structures confirm that a significant portion of the active site is disordered in the absence of a small molecule, as none of the NAD(+)-bound forms of the enzyme have ordered active sites. On the other hand, the NADH-bound form contains two small molecules in the active site: a phosphate and glycerol. The entire active site is ordered in the presence of these two molecules, completely encapsulating them within the interior cavity. Significant changes in the structure of the active site are also seen, including repositioning of the nicotinamide ring and a motion of a loop region to accommodate the bound phosphate. These changes call into question the mechanism previously proposed for the enzyme. A comparison of the yeast and mycobacterial enzymes shows a surprisingly large change in the relative orientation of the catalytic and Rossmann-fold domains in the two enzymes.
About this Structure
1P1H is a Single protein structure of sequence from Saccharomyces cerevisiae with as ligand. Active as Inositol-3-phosphate synthase, with EC number 5.5.1.4 Full crystallographic information is available from OCA.
Reference
Structures of NAD(+)- and NADH-bound 1-l-myo-inositol 1-phosphate synthase., Jin X, Geiger JH, Acta Crystallogr D Biol Crystallogr. 2003 Jul;59(Pt 7):1154-64. Epub 2003, Jun 27. PMID:12832758
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