8icd: Difference between revisions

Revision as of 20:17, 21 February 2008

REGULATION OF AN ENZYME BY PHOSPHORYLATION AT THE ACTIVE SITE

OverviewOverview

The isocitrate dehydrogenase of Escherichia coli is an example of a ubiquitous class of enzymes that are regulated by covalent modification. In the three-dimensional structure of the enzyme-substrate complex, isocitrate forms a hydrogen bond with Ser113, the site of regulatory phosphorylation. The structures of Asp113 and Glu113 mutants, which mimic the inactivation of the enzyme by phosphorylation, show minimal conformational changes from wild type, as in the phosphorylated enzyme. Calculations based on observed structures suggest that the change in electrostatic potential when a negative charge is introduced either by phosporylation or site-directed mutagenesis is sufficient to inactivate the enzyme. Thus, direct interaction at a ligand binding site is an alternative mechanism to induced conformational changes from an allosteric site in the regulation of protein activity by phosphorylation.

About this StructureAbout this Structure

8ICD is a Single protein structure of sequence from Escherichia coli with and as ligands. Active as Isocitrate dehydrogenase (NADP(+)), with EC number 1.1.1.42 Full crystallographic information is available from OCA.

ReferenceReference

Regulation of an enzyme by phosphorylation at the active site., Hurley JH, Dean AM, Sohl JL, Koshland DE Jr, Stroud RM, Science. 1990 Aug 31;249(4972):1012-6. PMID:2204109

Page seeded by OCA on Thu Feb 21 19:17:57 2008

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

OCA

@@ Line 1: / Line 1: @@
-[[Image:8icd.gif|left|200px]]<br /><applet load="8icd" size="450" color="white" frame="true" align="right" spinBox="true"
+[[Image:8icd.gif|left|200px]]<br /><applet load="8icd" size="350" color="white" frame="true" align="right" spinBox="true"
 caption="8icd, resolution 2.5&Aring;" />
 '''REGULATION OF AN ENZYME BY PHOSPHORYLATION AT THE ACTIVE SITE'''<br />
 ==Overview==
-The isocitrate dehydrogenase of Escherichia coli is an example of a, ubiquitous class of enzymes that are regulated by covalent modification., In the three-dimensional structure of the enzyme-substrate complex, isocitrate forms a hydrogen bond with Ser113, the site of regulatory, phosphorylation. The structures of Asp113 and Glu113 mutants, which mimic, the inactivation of the enzyme by phosphorylation, show minimal, conformational changes from wild type, as in the phosphorylated enzyme., Calculations based on observed structures suggest that the change in, electrostatic potential when a negative charge is introduced either by, phosporylation or site-directed mutagenesis is sufficient to inactivate, the enzyme. Thus, direct interaction at a ligand binding site is an, alternative mechanism to induced conformational changes from an allosteric, site in the regulation of protein activity by phosphorylation.
+The isocitrate dehydrogenase of Escherichia coli is an example of a ubiquitous class of enzymes that are regulated by covalent modification. In the three-dimensional structure of the enzyme-substrate complex, isocitrate forms a hydrogen bond with Ser113, the site of regulatory phosphorylation. The structures of Asp113 and Glu113 mutants, which mimic the inactivation of the enzyme by phosphorylation, show minimal conformational changes from wild type, as in the phosphorylated enzyme. Calculations based on observed structures suggest that the change in electrostatic potential when a negative charge is introduced either by phosporylation or site-directed mutagenesis is sufficient to inactivate the enzyme. Thus, direct interaction at a ligand binding site is an alternative mechanism to induced conformational changes from an allosteric site in the regulation of protein activity by phosphorylation.
 ==About this Structure==
-ICD 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 MG and ICT 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=8ICD OCA].
+ICD 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=MG:'>MG</scene> and <scene name='pdbligand=ICT:'>ICT</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=8ICD OCA].
 ==Reference==
@@ Line 14: / Line 14: @@
 [[Category: Isocitrate dehydrogenase (NADP(+))]]
 [[Category: Single protein]]
-[[Category: Dean, A.M.]]
+[[Category: Dean, A M.]]
-[[Category: Hurley, J.H.]]
+[[Category: Hurley, J H.]]
-[[Category: Koshlandjunior, D.E.]]
+[[Category: Koshlandjunior, D E.]]
-[[Category: Sohl, J.L.]]
+[[Category: Sohl, J L.]]
-[[Category: Stroud, R.M.]]
+[[Category: Stroud, R M.]]
 [[Category: ICT]]
 [[Category: MG]]
 [[Category: oxidoreductase (nad(a)-choh(d))]]
-''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Tue Nov 20 15:08:49 2007''
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 19:17:57 2008''