1pb3: Difference between revisions

New page: left|200px<br /><applet load="1pb3" size="450" color="white" frame="true" align="right" spinBox="true" caption="1pb3, resolution 1.70Å" /> '''Sites of binding and...
 
No edit summary
Line 1: Line 1:
[[Image:1pb3.jpg|left|200px]]<br /><applet load="1pb3" size="450" color="white" frame="true" align="right" spinBox="true"  
[[Image:1pb3.jpg|left|200px]]<br /><applet load="1pb3" size="350" color="white" frame="true" align="right" spinBox="true"  
caption="1pb3, resolution 1.70&Aring;" />
caption="1pb3, resolution 1.70&Aring;" />
'''Sites of binding and orientation in a four location model for protein stereospecificity.'''<br />
'''Sites of binding and orientation in a four location model for protein stereospecificity.'''<br />


==Overview==
==Overview==
The stereospecificity of the enzyme isocitrate dehydrogenase was examined, by steady-state kinetics and x-ray crystallography. The enzyme has the, intriguing property that the apoenzyme in the absence of divalent metal, showed a selectivity for the inactive l-enantiomer of the substrate, isocitrate, whereas the enzyme containing magnesium showed selectivity for, the physiologically active d-enantiomer. The hydrogen atom on the C2, carbon that is transferred during the reaction was, in both the d- and, l-isocitrate complexes, in an orientation very close to that expected for, delivery of a hydride ion to the cosubstrate NADP+. The beta-carboxylate, that is eliminated as a CO2 molecule during the reaction occupied the same, site on the protein in both the d- and l-isocitrate complexes. In, addition, the C3 carbon was in the same protein site in both the d- and, l-enantiomers. Only the fourth group, the OH atom, was in a very different, position in the apo enzyme and in the metal-containing complexes. A, four-location model is necessary to explain the enantiomeric specificity, of IDH in contrast to the conventional three-point attachment model. The, thermodynamic and kinetic ramifications of this model are explored.
The stereospecificity of the enzyme isocitrate dehydrogenase was examined by steady-state kinetics and x-ray crystallography. The enzyme has the intriguing property that the apoenzyme in the absence of divalent metal showed a selectivity for the inactive l-enantiomer of the substrate isocitrate, whereas the enzyme containing magnesium showed selectivity for the physiologically active d-enantiomer. The hydrogen atom on the C2 carbon that is transferred during the reaction was, in both the d- and l-isocitrate complexes, in an orientation very close to that expected for delivery of a hydride ion to the cosubstrate NADP+. The beta-carboxylate that is eliminated as a CO2 molecule during the reaction occupied the same site on the protein in both the d- and l-isocitrate complexes. In addition, the C3 carbon was in the same protein site in both the d- and l-enantiomers. Only the fourth group, the OH atom, was in a very different position in the apo enzyme and in the metal-containing complexes. A four-location model is necessary to explain the enantiomeric specificity of IDH in contrast to the conventional three-point attachment model. The thermodynamic and kinetic ramifications of this model are explored.


==About this Structure==
==About this Structure==
1PB3 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli] with SO4 and GOL as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Isocitrate_dehydrogenase_(NADP(+)) Isocitrate dehydrogenase (NADP(+))], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.1.1.42 1.1.1.42] Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1PB3 OCA].  
1PB3 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli] with <scene name='pdbligand=SO4:'>SO4</scene> and <scene name='pdbligand=GOL:'>GOL</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Isocitrate_dehydrogenase_(NADP(+)) Isocitrate dehydrogenase (NADP(+))], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.1.1.42 1.1.1.42] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1PB3 OCA].  


==Reference==
==Reference==
Line 14: Line 14:
[[Category: Isocitrate dehydrogenase (NADP(+))]]
[[Category: Isocitrate dehydrogenase (NADP(+))]]
[[Category: Single protein]]
[[Category: Single protein]]
[[Category: Jr., D.E.Koshland.]]
[[Category: Jr., D E.Koshland.]]
[[Category: Mesecar, A.D.]]
[[Category: Mesecar, A D.]]
[[Category: GOL]]
[[Category: GOL]]
[[Category: SO4]]
[[Category: SO4]]
Line 23: Line 23:
[[Category: stereospecificity]]
[[Category: stereospecificity]]


''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Tue Nov 20 23:39:10 2007''
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 14:26:58 2008''

Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

OCA