1ney: Difference between revisions
New page: left|200px<br /><applet load="1ney" size="450" color="white" frame="true" align="right" spinBox="true" caption="1ney, resolution 1.20Å" /> '''Triosephosphate Isom... |
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[[Image:1ney.jpg|left|200px]]<br /><applet load="1ney" size=" | [[Image:1ney.jpg|left|200px]]<br /><applet load="1ney" size="350" color="white" frame="true" align="right" spinBox="true" | ||
caption="1ney, resolution 1.20Å" /> | caption="1ney, resolution 1.20Å" /> | ||
'''Triosephosphate Isomerase in Complex with DHAP'''<br /> | '''Triosephosphate Isomerase in Complex with DHAP'''<br /> | ||
==Overview== | ==Overview== | ||
In enzyme catalysis, where exquisitely positioned functionality is the | In enzyme catalysis, where exquisitely positioned functionality is the sine qua non, atomic coordinates for a Michaelis complex can provide powerful insights into activation of the substrate. We focus here on the initial proton transfer of the isomerization reaction catalyzed by triosephosphate isomerase and present the crystal structure of its Michaelis complex with the substrate dihydroxyacetone phosphate at near-atomic resolution. The active site is highly compact, with unusually short and bifurcated hydrogen bonds for both catalytic Glu-165 and His-95 residues. The carboxylate oxygen of the catalytic base Glu-165 is positioned in an unprecedented close interaction with the ketone and the alpha-hydroxy carbons of the substrate (C em leader O approximately 3.0 A), which is optimal for the proton transfer involving these centers. The electrophile that polarizes the substrate, His-95, has close contacts to the substrate's O1 and O2 (N em leader O < or = 3.0 and 2.6 A, respectively). The substrate is conformationally relaxed in the Michaelis complex: the phosphate group is out of the plane of the ketone group, and the hydroxy and ketone oxygen atoms are not in the cisoid configuration. The epsilon ammonium group of the electrophilic Lys-12 is within hydrogen-bonding distance of the substrate's ketone oxygen, the bridging oxygen, and a terminal phosphate's oxygen, suggesting a role for this residue in both catalysis and in controlling the flexibility of active-site loop. | ||
==About this Structure== | ==About this Structure== | ||
1NEY 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 13P as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [http://en.wikipedia.org/wiki/Triose-phosphate_isomerase Triose-phosphate isomerase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=5.3.1.1 5.3.1.1] Full crystallographic information is available from [http:// | 1NEY 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=13P:'>13P</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [http://en.wikipedia.org/wiki/Triose-phosphate_isomerase Triose-phosphate isomerase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=5.3.1.1 5.3.1.1] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1NEY OCA]. | ||
==Reference== | ==Reference== | ||
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[[Category: Triose-phosphate isomerase]] | [[Category: Triose-phosphate isomerase]] | ||
[[Category: Jogl, G.]] | [[Category: Jogl, G.]] | ||
[[Category: McDermott, A | [[Category: McDermott, A E.]] | ||
[[Category: Rozovsky, S.]] | [[Category: Rozovsky, S.]] | ||
[[Category: Tong, L.]] | [[Category: Tong, L.]] | ||
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[[Category: yeast]] | [[Category: yeast]] | ||
''Page seeded by [http:// | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 14:05:21 2008'' | ||
Revision as of 15:05, 21 February 2008
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Triosephosphate Isomerase in Complex with DHAP
OverviewOverview
In enzyme catalysis, where exquisitely positioned functionality is the sine qua non, atomic coordinates for a Michaelis complex can provide powerful insights into activation of the substrate. We focus here on the initial proton transfer of the isomerization reaction catalyzed by triosephosphate isomerase and present the crystal structure of its Michaelis complex with the substrate dihydroxyacetone phosphate at near-atomic resolution. The active site is highly compact, with unusually short and bifurcated hydrogen bonds for both catalytic Glu-165 and His-95 residues. The carboxylate oxygen of the catalytic base Glu-165 is positioned in an unprecedented close interaction with the ketone and the alpha-hydroxy carbons of the substrate (C em leader O approximately 3.0 A), which is optimal for the proton transfer involving these centers. The electrophile that polarizes the substrate, His-95, has close contacts to the substrate's O1 and O2 (N em leader O < or = 3.0 and 2.6 A, respectively). The substrate is conformationally relaxed in the Michaelis complex: the phosphate group is out of the plane of the ketone group, and the hydroxy and ketone oxygen atoms are not in the cisoid configuration. The epsilon ammonium group of the electrophilic Lys-12 is within hydrogen-bonding distance of the substrate's ketone oxygen, the bridging oxygen, and a terminal phosphate's oxygen, suggesting a role for this residue in both catalysis and in controlling the flexibility of active-site loop.
About this StructureAbout this Structure
1NEY is a Single protein structure of sequence from Saccharomyces cerevisiae with as ligand. Active as Triose-phosphate isomerase, with EC number 5.3.1.1 Full crystallographic information is available from OCA.
ReferenceReference
Optimal alignment for enzymatic proton transfer: structure of the Michaelis complex of triosephosphate isomerase at 1.2-A resolution., Jogl G, Rozovsky S, McDermott AE, Tong L, Proc Natl Acad Sci U S A. 2003 Jan 7;100(1):50-5. Epub 2002 Dec 30. PMID:12509510
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