2gd1: Difference between revisions

Revision as of 18:30, 21 February 2008

COENZYME-INDUCED CONFORMATIONAL CHANGES IN GLYCERALDEHYDE-3-PHOSPHATE DEHYDROGENASE FROM BACILLUS STEAROTHERMOPHILLUS

OverviewOverview

The structure of apo-glyceraldehyde-3-phosphate dehydrogenase (GAPDHase) from Bacillus stearothermophilus has been refined using a restrained least-squares method. The final crystallographic R-factor is 0.177 for all 53,315 reflections between 7.0 and 2.5 A. The resulting model has been analysed with respect to lattice interactions, molecular symmetry, temperature factors and solvent structure showing that, apart from local deviations due to intermolecular contact, the molecule exhibits a very high degree of local 222 symmetry. Analysis of differences between the structure of apo-GAPDHase and the previously refined holo-GAPDHase at 1.8 A resolution reveals details of conformational change in the enzyme induced by cofactor binding. The change, which was previously described as a rigid-body rotation of the coenzyme-binding domain with respect to the catalytic domain, is of more complex nature and involves relative shifts of several structural elements in the coenzyme-binding domain and some small changes in the catalytic domain. A possible mechanism of this conformational change is proposed based on the comparison of the refined structures and model-building studies. According to this mechanism, the adenosine moiety of NAD can initially bind to the protein in the apo-enzyme conformation. Several attractive interactions resulting from the initial binding of the coenzyme trigger conformational changes in the molecule of GAPDHase that: (1) create the productive nicotinamide-moiety binding site; (2) improve enzyme-coenzyme interactions at the adenosine moiety; (3) modify the active site to optimize the positioning of catalytic residues and ion-binding sites. Implications of the proposed mechanism for existing experimental data on binding of NAD analogues to GAPDHase are discussed.

About this StructureAbout this Structure

2GD1 is a Single protein structure of sequence from Geobacillus stearothermophilus with as ligand. Active as Glyceraldehyde-3-phosphate dehydrogenase (phosphorylating), with EC number 1.2.1.12 Full crystallographic information is available from OCA.

ReferenceReference

Coenzyme-induced conformational changes in glyceraldehyde-3-phosphate dehydrogenase from Bacillus stearothermophilus., Skarzynski T, Wonacott AJ, J Mol Biol. 1988 Oct 20;203(4):1097-118. PMID:3210237

Page seeded by OCA on Thu Feb 21 17:30:31 2008

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

OCA

@@ Line 1: / Line 1: @@
-[[Image:2gd1.jpg|left|200px]]<br /><applet load="2gd1" size="450" color="white" frame="true" align="right" spinBox="true"
+[[Image:2gd1.jpg|left|200px]]<br /><applet load="2gd1" size="350" color="white" frame="true" align="right" spinBox="true"
 caption="2gd1, resolution 2.5&Aring;" />
 '''COENZYME-INDUCED CONFORMATIONAL CHANGES IN GLYCERALDEHYDE-3-PHOSPHATE DEHYDROGENASE FROM BACILLUS STEAROTHERMOPHILLUS'''<br />
 ==Overview==
-The structure of apo-glyceraldehyde-3-phosphate dehydrogenase (GAPDHase), from Bacillus stearothermophilus has been refined using a restrained, least-squares method. The final crystallographic R-factor is 0.177 for all, 53,315 reflections between 7.0 and 2.5 A. The resulting model has been, analysed with respect to lattice interactions, molecular symmetry, temperature factors and solvent structure showing that, apart from local, deviations due to intermolecular contact, the molecule exhibits a very, high degree of local 222 symmetry. Analysis of differences between the, structure of apo-GAPDHase and the previously refined holo-GAPDHase at 1.8, A resolution reveals details of conformational change in the enzyme, induced by cofactor binding. The change, which was previously described as, a rigid-body rotation of the coenzyme-binding domain with respect to the, catalytic domain, is of more complex nature and involves relative shifts, of several structural elements in the coenzyme-binding domain and some, small changes in the catalytic domain. A possible mechanism of this, conformational change is proposed based on the comparison of the refined, structures and model-building studies. According to this mechanism, the, adenosine moiety of NAD can initially bind to the protein in the, apo-enzyme conformation. Several attractive interactions resulting from, the initial binding of the coenzyme trigger conformational changes in the, molecule of GAPDHase that: (1) create the productive nicotinamide-moiety, binding site; (2) improve enzyme-coenzyme interactions at the adenosine, moiety; (3) modify the active site to optimize the positioning of, catalytic residues and ion-binding sites. Implications of the proposed, mechanism for existing experimental data on binding of NAD analogues to, GAPDHase are discussed.
+The structure of apo-glyceraldehyde-3-phosphate dehydrogenase (GAPDHase) from Bacillus stearothermophilus has been refined using a restrained least-squares method. The final crystallographic R-factor is 0.177 for all 53,315 reflections between 7.0 and 2.5 A. The resulting model has been analysed with respect to lattice interactions, molecular symmetry, temperature factors and solvent structure showing that, apart from local deviations due to intermolecular contact, the molecule exhibits a very high degree of local 222 symmetry. Analysis of differences between the structure of apo-GAPDHase and the previously refined holo-GAPDHase at 1.8 A resolution reveals details of conformational change in the enzyme induced by cofactor binding. The change, which was previously described as a rigid-body rotation of the coenzyme-binding domain with respect to the catalytic domain, is of more complex nature and involves relative shifts of several structural elements in the coenzyme-binding domain and some small changes in the catalytic domain. A possible mechanism of this conformational change is proposed based on the comparison of the refined structures and model-building studies. According to this mechanism, the adenosine moiety of NAD can initially bind to the protein in the apo-enzyme conformation. Several attractive interactions resulting from the initial binding of the coenzyme trigger conformational changes in the molecule of GAPDHase that: (1) create the productive nicotinamide-moiety binding site; (2) improve enzyme-coenzyme interactions at the adenosine moiety; (3) modify the active site to optimize the positioning of catalytic residues and ion-binding sites. Implications of the proposed mechanism for existing experimental data on binding of NAD analogues to GAPDHase are discussed.
 ==About this Structure==
-GD1 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Geobacillus_stearothermophilus Geobacillus stearothermophilus] with SO4 as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [http://en.wikipedia.org/wiki/Glyceraldehyde-3-phosphate_dehydrogenase_(phosphorylating) Glyceraldehyde-3-phosphate dehydrogenase (phosphorylating)], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.2.1.12 1.2.1.12] Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=2GD1 OCA].
+GD1 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Geobacillus_stearothermophilus Geobacillus stearothermophilus] with <scene name='pdbligand=SO4:'>SO4</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [http://en.wikipedia.org/wiki/Glyceraldehyde-3-phosphate_dehydrogenase_(phosphorylating) Glyceraldehyde-3-phosphate dehydrogenase (phosphorylating)], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.2.1.12 1.2.1.12] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2GD1 OCA].
 ==Reference==
@@ Line 15: / Line 15: @@
 [[Category: Single protein]]
 [[Category: Skarzynski, T.]]
-[[Category: Wonacott, A.J.]]
+[[Category: Wonacott, A J.]]
 [[Category: SO4]]
 [[Category: oxidoreductase(aldehyde(d)-nad(a))]]
-''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Wed Nov 21 11:07:57 2007''
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 17:30:31 2008''