1yz0
From Proteopedia
(New page: 200px<br /><applet load="1yz0" size="450" color="white" frame="true" align="right" spinBox="true" caption="1yz0, resolution 2.07Å" /> '''R-State AMP Complex ...) |
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| - | [[Image:1yz0.gif|left|200px]]<br /><applet load="1yz0" size=" | + | [[Image:1yz0.gif|left|200px]]<br /><applet load="1yz0" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="1yz0, resolution 2.07Å" /> | caption="1yz0, resolution 2.07Å" /> | ||
'''R-State AMP Complex Reveals Initial Steps of the Quaternary Transition of Fructose-1,6-bisphosphatase'''<br /> | '''R-State AMP Complex Reveals Initial Steps of the Quaternary Transition of Fructose-1,6-bisphosphatase'''<br /> | ||
==Overview== | ==Overview== | ||
| - | AMP transforms fructose-1,6-bisphosphatase from its active R-state to its | + | AMP transforms fructose-1,6-bisphosphatase from its active R-state to its inactive T-state; however, the mechanism of that transformation is poorly understood. The mutation of Ala(54) to leucine destabilizes the T-state of fructose-1,6-bisphosphatase. The mutant enzyme retains wild-type levels of activity, but the concentration of AMP that causes 50% inhibition increases 50-fold. In the absence of AMP, the Leu(54) enzyme adopts an R-state conformation nearly identical to that of the wild-type enzyme. The mutant enzyme, however, grows in two crystal forms in the presence of saturating AMP. In one form, the AMP-bound tetramer is in a T-like conformation, whereas in the other form, the AMP-bound tetramer is in a R-like conformation. The latter reveals conformational changes in two helices due to the binding of AMP. Helix H1 moves toward the center of the tetramer and displaces Ile(10) from a hydrophobic pocket. The displacement of Ile(10) exposes a hydrophobic surface critical to interactions that stabilize the T-state. Helix H2 moves away from the center of the tetramer, breaking hydrogen bonds with a buried loop (residues 187-195) in an adjacent subunit. The same hydrogen bonds reform but only after the quaternary transition to the T-state. Proposed here is a model that accounts for the quaternary transition and cooperativity in the inhibition of catalysis by AMP. |
==About this Structure== | ==About this Structure== | ||
| - | 1YZ0 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Sus_scrofa Sus scrofa] with F6P, MG and AMP as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Fructose-bisphosphatase Fructose-bisphosphatase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.1.3.11 3.1.3.11] Full crystallographic information is available from [http:// | + | 1YZ0 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Sus_scrofa Sus scrofa] with <scene name='pdbligand=F6P:'>F6P</scene>, <scene name='pdbligand=MG:'>MG</scene> and <scene name='pdbligand=AMP:'>AMP</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Fructose-bisphosphatase Fructose-bisphosphatase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.1.3.11 3.1.3.11] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1YZ0 OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Single protein]] | [[Category: Single protein]] | ||
[[Category: Sus scrofa]] | [[Category: Sus scrofa]] | ||
| - | [[Category: Fromm, H | + | [[Category: Fromm, H J.]] |
| - | [[Category: Honzatko, R | + | [[Category: Honzatko, R B.]] |
| - | [[Category: Iancu, C | + | [[Category: Iancu, C V.]] |
[[Category: Mukund, S.]] | [[Category: Mukund, S.]] | ||
[[Category: AMP]] | [[Category: AMP]] | ||
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[[Category: allosteric enzymes; intermediate states; glycolysis; gluconeogenesis]] | [[Category: allosteric enzymes; intermediate states; glycolysis; gluconeogenesis]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 16:10:31 2008'' |
Revision as of 14:10, 21 February 2008
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R-State AMP Complex Reveals Initial Steps of the Quaternary Transition of Fructose-1,6-bisphosphatase
Overview
AMP transforms fructose-1,6-bisphosphatase from its active R-state to its inactive T-state; however, the mechanism of that transformation is poorly understood. The mutation of Ala(54) to leucine destabilizes the T-state of fructose-1,6-bisphosphatase. The mutant enzyme retains wild-type levels of activity, but the concentration of AMP that causes 50% inhibition increases 50-fold. In the absence of AMP, the Leu(54) enzyme adopts an R-state conformation nearly identical to that of the wild-type enzyme. The mutant enzyme, however, grows in two crystal forms in the presence of saturating AMP. In one form, the AMP-bound tetramer is in a T-like conformation, whereas in the other form, the AMP-bound tetramer is in a R-like conformation. The latter reveals conformational changes in two helices due to the binding of AMP. Helix H1 moves toward the center of the tetramer and displaces Ile(10) from a hydrophobic pocket. The displacement of Ile(10) exposes a hydrophobic surface critical to interactions that stabilize the T-state. Helix H2 moves away from the center of the tetramer, breaking hydrogen bonds with a buried loop (residues 187-195) in an adjacent subunit. The same hydrogen bonds reform but only after the quaternary transition to the T-state. Proposed here is a model that accounts for the quaternary transition and cooperativity in the inhibition of catalysis by AMP.
About this Structure
1YZ0 is a Single protein structure of sequence from Sus scrofa with , and as ligands. Active as Fructose-bisphosphatase, with EC number 3.1.3.11 Full crystallographic information is available from OCA.
Reference
R-state AMP complex reveals initial steps of the quaternary transition of fructose-1,6-bisphosphatase., Iancu CV, Mukund S, Fromm HJ, Honzatko RB, J Biol Chem. 2005 May 20;280(20):19737-45. Epub 2005 Mar 14. PMID:15767255
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