4gpb: Difference between revisions

Revision as of 20:13, 21 February 2008

COMPARISON OF THE BINDING OF GLUCOSE AND GLUCOSE-1-PHOSPHATE DERIVATIVES TO T-STATE GLYCOGEN PHOSPHORYLASE B

OverviewOverview

The binding of T-state- and R-state-stabilizing ligands to the catalytic C site of T-state glycogen phosphorylase b has been investigated by crystallographic methods to study the interactions made and the conformational changes that occur at the C site. The compounds studied were alpha-D-glucose, 1, a T-state-stabilizing inhibitor of the enzyme, and the R-state-stabilizing phosphorylated ligands alpha-D-glucose 1-phosphate (2), 2-deoxy-2-fluoro-alpha-D-glucose 1-phosphate (3), and alpha-D-glucose 1-methylenephosphonate (4). The complexes have been refined, giving crystallographic R factors of less than 19%, for data between 8 and 2.3 A. Analysis of the refined structures shows that the glucosyl portions of the phosphorylated ligands bind in the same orientation as glucose and retain most of the interactions formed between glucose and the enzyme. However, the phosphates of the phosphorylated ligands adopt different conformations in each case; the stability of these conformations have been studied by using computational methods to rationalize the different binding modes. Binding of the phosphorylated ligands is accompanied by movement of C-site residues, most notably a shift of a loop out of the C site and toward the exterior of the protein. The C-site alterations do not include movement of Arg569, which has been observed in both the refined complex with 1-deoxy-D-gluco-heptulose 2-phosphate (5) [Johnson, L. N., et al (1990) J. Mol. Biol. 211, 645-661] and in the R-state enzyme [Barford, D. & Johnson, L. N. (1989) Nature 340, 609-616]. Refinement of the ligand complexes has also led to the observation of additional electron density for residues 10-19 at the N-terminus which had not previously been localized in the native structure. The conformation of this stretch of residues is different from that observed in glycogen phosphorylase a.

About this StructureAbout this Structure

4GPB is a Single protein structure of sequence from Oryctolagus cuniculus with and as ligands. Active as Phosphorylase, with EC number 2.4.1.1 Full crystallographic information is available from OCA.

ReferenceReference

Comparison of the binding of glucose and glucose 1-phosphate derivatives to T-state glycogen phosphorylase b., Martin JL, Johnson LN, Withers SG, Biochemistry. 1990 Dec 4;29(48):10745-57. PMID:2125493

Page seeded by OCA on Thu Feb 21 19:13:23 2008

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

OCA

@@ Line 1: / Line 1: @@
-[[Image:4gpb.gif|left|200px]]<br /><applet load="4gpb" size="450" color="white" frame="true" align="right" spinBox="true"
+[[Image:4gpb.gif|left|200px]]<br /><applet load="4gpb" size="350" color="white" frame="true" align="right" spinBox="true"
 caption="4gpb, resolution 2.3&Aring;" />
 '''COMPARISON OF THE BINDING OF GLUCOSE AND GLUCOSE-1-PHOSPHATE DERIVATIVES TO T-STATE GLYCOGEN PHOSPHORYLASE B'''<br />
 ==Overview==
-The binding of T-state- and R-state-stabilizing ligands to the catalytic C, site of T-state glycogen phosphorylase b has been investigated by, crystallographic methods to study the interactions made and the, conformational changes that occur at the C site. The compounds studied, were alpha-D-glucose, 1, a T-state-stabilizing inhibitor of the enzyme, and the R-state-stabilizing phosphorylated ligands alpha-D-glucose, 1-phosphate (2), 2-deoxy-2-fluoro-alpha-D-glucose 1-phosphate (3), and, alpha-D-glucose 1-methylenephosphonate (4). The complexes have been, refined, giving crystallographic R factors of less than 19%, for data, between 8 and 2.3 A. Analysis of the refined structures shows that the, glucosyl portions of the phosphorylated ligands bind in the same, orientation as glucose and retain most of the interactions formed between, glucose and the enzyme. However, the phosphates of the phosphorylated, ligands adopt different conformations in each case; the stability of these, conformations have been studied by using computational methods to, rationalize the different binding modes. Binding of the phosphorylated, ligands is accompanied by movement of C-site residues, most notably a, shift of a loop out of the C site and toward the exterior of the protein., The C-site alterations do not include movement of Arg569, which has been, observed in both the refined complex with 1-deoxy-D-gluco-heptulose, 2-phosphate (5) [Johnson, L. N., et al (1990) J. Mol. Biol. 211, 645-661], and in the R-state enzyme [Barford, D. &amp; Johnson, L. N. (1989) Nature 340, 609-616]. Refinement of the ligand complexes has also led to the, observation of additional electron density for residues 10-19 at the, N-terminus which had not previously been localized in the native, structure. The conformation of this stretch of residues is different from, that observed in glycogen phosphorylase a.
+The binding of T-state- and R-state-stabilizing ligands to the catalytic C site of T-state glycogen phosphorylase b has been investigated by crystallographic methods to study the interactions made and the conformational changes that occur at the C site. The compounds studied were alpha-D-glucose, 1, a T-state-stabilizing inhibitor of the enzyme, and the R-state-stabilizing phosphorylated ligands alpha-D-glucose 1-phosphate (2), 2-deoxy-2-fluoro-alpha-D-glucose 1-phosphate (3), and alpha-D-glucose 1-methylenephosphonate (4). The complexes have been refined, giving crystallographic R factors of less than 19%, for data between 8 and 2.3 A. Analysis of the refined structures shows that the glucosyl portions of the phosphorylated ligands bind in the same orientation as glucose and retain most of the interactions formed between glucose and the enzyme. However, the phosphates of the phosphorylated ligands adopt different conformations in each case; the stability of these conformations have been studied by using computational methods to rationalize the different binding modes. Binding of the phosphorylated ligands is accompanied by movement of C-site residues, most notably a shift of a loop out of the C site and toward the exterior of the protein. The C-site alterations do not include movement of Arg569, which has been observed in both the refined complex with 1-deoxy-D-gluco-heptulose 2-phosphate (5) [Johnson, L. N., et al (1990) J. Mol. Biol. 211, 645-661] and in the R-state enzyme [Barford, D. &amp; Johnson, L. N. (1989) Nature 340, 609-616]. Refinement of the ligand complexes has also led to the observation of additional electron density for residues 10-19 at the N-terminus which had not previously been localized in the native structure. The conformation of this stretch of residues is different from that observed in glycogen phosphorylase a.
 ==About this Structure==
-GPB is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Oryctolagus_cuniculus Oryctolagus cuniculus] with GFP and PLP as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Phosphorylase Phosphorylase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.4.1.1 2.4.1.1] Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=4GPB OCA].
+GPB is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Oryctolagus_cuniculus Oryctolagus cuniculus] with <scene name='pdbligand=GFP:'>GFP</scene> and <scene name='pdbligand=PLP:'>PLP</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Phosphorylase Phosphorylase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.4.1.1 2.4.1.1] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4GPB OCA].
 ==Reference==
@@ Line 14: / Line 14: @@
 [[Category: Phosphorylase]]
 [[Category: Single protein]]
-[[Category: Johnson, L.N.]]
+[[Category: Johnson, L N.]]
-[[Category: Martin, J.L.]]
+[[Category: Martin, J L.]]
 [[Category: GFP]]
 [[Category: PLP]]
 [[Category: glycogen phosphorylase]]
-''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Tue Nov 20 19:37:46 2007''
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 19:13:23 2008''