1p1j: Difference between revisions

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New page: left|200px<br /><applet load="1p1j" size="450" color="white" frame="true" align="right" spinBox="true" caption="1p1j, resolution 1.7Å" /> '''Crystal structure of ...
 
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[[Image:1p1j.jpg|left|200px]]<br /><applet load="1p1j" size="450" color="white" frame="true" align="right" spinBox="true"  
[[Image:1p1j.jpg|left|200px]]<br /><applet load="1p1j" size="350" color="white" frame="true" align="right" spinBox="true"  
caption="1p1j, resolution 1.7&Aring;" />
caption="1p1j, resolution 1.7&Aring;" />
'''Crystal structure of the 1L-myo-inositol 1-phosphate synthase complexed with NADH'''<br />
'''Crystal structure of the 1L-myo-inositol 1-phosphate synthase complexed with NADH'''<br />


==Overview==
==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.
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==
1P1J 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 PO4, NAI and GOL 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=1P1J OCA].  
1P1J 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=PO4:'>PO4</scene>, <scene name='pdbligand=NAI:'>NAI</scene> and <scene name='pdbligand=GOL:'>GOL</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=1P1J OCA].  


==Reference==
==Reference==
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[[Category: Saccharomyces cerevisiae]]
[[Category: Saccharomyces cerevisiae]]
[[Category: Single protein]]
[[Category: Single protein]]
[[Category: Geiger, J.H.]]
[[Category: Geiger, J H.]]
[[Category: Jin, X.]]
[[Category: Jin, X.]]
[[Category: GOL]]
[[Category: GOL]]
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[[Category: rossmann fold]]
[[Category: rossmann fold]]


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