1u0f: Difference between revisions
New page: left|200px<br /><applet load="1u0f" size="450" color="white" frame="true" align="right" spinBox="true" caption="1u0f, resolution 1.60Å" /> '''Crystal structure of... |
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[[Image:1u0f.jpg|left|200px]]<br /><applet load="1u0f" size=" | [[Image:1u0f.jpg|left|200px]]<br /><applet load="1u0f" size="350" color="white" frame="true" align="right" spinBox="true" | ||
caption="1u0f, resolution 1.60Å" /> | caption="1u0f, resolution 1.60Å" /> | ||
'''Crystal structure of mouse phosphoglucose isomerase in complex with glucose 6-phosphate'''<br /> | '''Crystal structure of mouse phosphoglucose isomerase in complex with glucose 6-phosphate'''<br /> | ||
==Overview== | ==Overview== | ||
Phosphoglucose isomerase (PGI) is an enzyme of glycolysis that | Phosphoglucose isomerase (PGI) is an enzyme of glycolysis that interconverts glucose 6-phosphate (G6P) and fructose 6-phosphate (F6P) but, outside the cell, is a multifunctional cytokine. High-resolution crystal structures of the enzyme from mouse have been determined in native form and in complex with the inhibitor erythrose 4-phosphate, and with the substrate glucose 6-phosphate. In the substrate-bound structure, the glucose sugar is observed in both straight-chain and ring forms. This structure supports a specific role for Lys518 in enzyme-catalyzed ring opening and we present a "push-pull" mechanism in which His388 breaks the O5-C1 bond by donating a proton to the ring oxygen atom and, simultaneously, Lys518 abstracts a proton from the C1 hydroxyl group. The reverse occurs in ring closure. The transition from ring form to straight-chain substrate is achieved through rotation of the C3-C4 bond, which brings the C1-C2 region into close proximity to Glu357, the base catalyst for the isomerization step. The structure with G6P also explains the specificity of PGI for glucose 6-phosphate over mannose 6-isomerase (M6P). To isomerize M6P to F6P requires a rotation of its C2-C3 bond but in PGI this is sterically blocked by Gln511. | ||
==About this Structure== | ==About this Structure== | ||
1U0F is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus] with G6P, G6Q, SO4, BME and GOL as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Glucose-6-phosphate_isomerase Glucose-6-phosphate isomerase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=5.3.1.9 5.3.1.9] Full crystallographic information is available from [http:// | 1U0F is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus] with <scene name='pdbligand=G6P:'>G6P</scene>, <scene name='pdbligand=G6Q:'>G6Q</scene>, <scene name='pdbligand=SO4:'>SO4</scene>, <scene name='pdbligand=BME:'>BME</scene> and <scene name='pdbligand=GOL:'>GOL</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Glucose-6-phosphate_isomerase Glucose-6-phosphate isomerase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=5.3.1.9 5.3.1.9] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1U0F OCA]. | ||
==Reference== | ==Reference== | ||
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[[Category: Krishnamurthy, N.]] | [[Category: Krishnamurthy, N.]] | ||
[[Category: Muirhead, H.]] | [[Category: Muirhead, H.]] | ||
[[Category: Solomons, J | [[Category: Solomons, J T.G.]] | ||
[[Category: Swan, M | [[Category: Swan, M K.]] | ||
[[Category: Zimmerly, E | [[Category: Zimmerly, E M.]] | ||
[[Category: BME]] | [[Category: BME]] | ||
[[Category: G6P]] | [[Category: G6P]] | ||
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[[Category: dimer]] | [[Category: dimer]] | ||
''Page seeded by [http:// | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 15:19:20 2008'' | ||
Revision as of 16:19, 21 February 2008
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Crystal structure of mouse phosphoglucose isomerase in complex with glucose 6-phosphate
OverviewOverview
Phosphoglucose isomerase (PGI) is an enzyme of glycolysis that interconverts glucose 6-phosphate (G6P) and fructose 6-phosphate (F6P) but, outside the cell, is a multifunctional cytokine. High-resolution crystal structures of the enzyme from mouse have been determined in native form and in complex with the inhibitor erythrose 4-phosphate, and with the substrate glucose 6-phosphate. In the substrate-bound structure, the glucose sugar is observed in both straight-chain and ring forms. This structure supports a specific role for Lys518 in enzyme-catalyzed ring opening and we present a "push-pull" mechanism in which His388 breaks the O5-C1 bond by donating a proton to the ring oxygen atom and, simultaneously, Lys518 abstracts a proton from the C1 hydroxyl group. The reverse occurs in ring closure. The transition from ring form to straight-chain substrate is achieved through rotation of the C3-C4 bond, which brings the C1-C2 region into close proximity to Glu357, the base catalyst for the isomerization step. The structure with G6P also explains the specificity of PGI for glucose 6-phosphate over mannose 6-isomerase (M6P). To isomerize M6P to F6P requires a rotation of its C2-C3 bond but in PGI this is sterically blocked by Gln511.
About this StructureAbout this Structure
1U0F is a Single protein structure of sequence from Mus musculus with , , , and as ligands. Active as Glucose-6-phosphate isomerase, with EC number 5.3.1.9 Full crystallographic information is available from OCA.
ReferenceReference
The crystal structure of mouse phosphoglucose isomerase at 1.6A resolution and its complex with glucose 6-phosphate reveals the catalytic mechanism of sugar ring opening., Graham Solomons JT, Zimmerly EM, Burns S, Krishnamurthy N, Swan MK, Krings S, Muirhead H, Chirgwin J, Davies C, J Mol Biol. 2004 Sep 17;342(3):847-60. PMID:15342241
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