182l: Difference between revisions

Revision as of 12:39, 21 February 2008

SPECIFICITY OF LIGAND BINDING IN A BURIED NON-POLAR CAVITY OF T4 LYSOZYME: LINKAGE OF DYNAMICS AND STRUCTURAL PLASTICITY

OverviewOverview

To better understand the role of shape complementarity in ligand binding and protein core interactions, the structures have been determined of a set of ligands bound within a cavity-containing mutant of T4 lysozyme. The interior cavity is seen to consist of two parts that respond very differently to the binding of ligands. First, there is a relatively rigid region that does not relax significantly upon binding any ligand. Second, there is a more flexible region that moves to various extents in response to binding the different ligands. The part of the binding site that remains rigid is characterized by low temperature factors and strong protection from hydrogen exchange. This part of the site appears to be primarily responsible for discriminating between ligands of different shape (i.e., for determining specificity). The more flexible region, characterized by relatively high temperature factors and weak protection from hydrogen exchange, allows some promiscuity in binding by undergoing variable amounts of deformation at essentially the same energetic cost. This linkage between the dynamic information represented by crystallographic temperature factors and hydrogen-exchange behavior on the one hand, and structural plasticity in response to ligand binding on the other hand, suggests a way to improve our understanding of steric interactions in protein cores and protein-ligand binding sites. Ligand design and packing algorithms might take advantage of this information, requiring complementary interactions where the protein is rigid and allowing some overlap in regions where the protein is flexible.

About this StructureAbout this Structure

182L is a Single protein structure of sequence from Enterobacteria phage t2 with , and as ligands. Active as Lysozyme, with EC number 3.2.1.17 Full crystallographic information is available from OCA.

ReferenceReference

Specificity of ligand binding in a buried nonpolar cavity of T4 lysozyme: linkage of dynamics and structural plasticity., Morton A, Matthews BW, Biochemistry. 1995 Jul 11;34(27):8576-88. PMID:7612599

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OCA

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-[[Image:182l.gif|left|200px]]<br /><applet load="182l" size="450" color="white" frame="true" align="right" spinBox="true"
+[[Image:182l.gif|left|200px]]<br /><applet load="182l" size="350" color="white" frame="true" align="right" spinBox="true"
 caption="182l, resolution 1.80&Aring;" />
 '''SPECIFICITY OF LIGAND BINDING IN A BURIED NON-POLAR CAVITY OF T4 LYSOZYME: LINKAGE OF DYNAMICS AND STRUCTURAL PLASTICITY'''<br />
 ==Overview==
-To better understand the role of shape complementarity in ligand binding, and protein core interactions, the structures have been determined of a, set of ligands bound within a cavity-containing mutant of T4 lysozyme. The, interior cavity is seen to consist of two parts that respond very, differently to the binding of ligands. First, there is a relatively rigid, region that does not relax significantly upon binding any ligand. Second, there is a more flexible region that moves to various extents in response, to binding the different ligands. The part of the binding site that, remains rigid is characterized by low temperature factors and strong, protection from hydrogen exchange. This part of the site appears to be, primarily responsible for discriminating between ligands of different, shape (i.e., for determining specificity). The more flexible region, characterized by relatively high temperature factors and weak protection, from hydrogen exchange, allows some promiscuity in binding by undergoing, variable amounts of deformation at essentially the same energetic cost., This linkage between the dynamic information represented by, crystallographic temperature factors and hydrogen-exchange behavior on the, one hand, and structural plasticity in response to ligand binding on the, other hand, suggests a way to improve our understanding of steric, interactions in protein cores and protein-ligand binding sites. Ligand, design and packing algorithms might take advantage of this information, requiring complementary interactions where the protein is rigid and, allowing some overlap in regions where the protein is flexible.
+To better understand the role of shape complementarity in ligand binding and protein core interactions, the structures have been determined of a set of ligands bound within a cavity-containing mutant of T4 lysozyme. The interior cavity is seen to consist of two parts that respond very differently to the binding of ligands. First, there is a relatively rigid region that does not relax significantly upon binding any ligand. Second, there is a more flexible region that moves to various extents in response to binding the different ligands. The part of the binding site that remains rigid is characterized by low temperature factors and strong protection from hydrogen exchange. This part of the site appears to be primarily responsible for discriminating between ligands of different shape (i.e., for determining specificity). The more flexible region, characterized by relatively high temperature factors and weak protection from hydrogen exchange, allows some promiscuity in binding by undergoing variable amounts of deformation at essentially the same energetic cost. This linkage between the dynamic information represented by crystallographic temperature factors and hydrogen-exchange behavior on the one hand, and structural plasticity in response to ligand binding on the other hand, suggests a way to improve our understanding of steric interactions in protein cores and protein-ligand binding sites. Ligand design and packing algorithms might take advantage of this information, requiring complementary interactions where the protein is rigid and allowing some overlap in regions where the protein is flexible.
 ==About this Structure==
-L is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Enterobacteria_phage_t2 Enterobacteria phage t2] with CL, HED and BZF as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Lysozyme Lysozyme], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.2.1.17 3.2.1.17] Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=182L OCA].
+L is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Enterobacteria_phage_t2 Enterobacteria phage t2] with <scene name='pdbligand=CL:'>CL</scene>, <scene name='pdbligand=HED:'>HED</scene> and <scene name='pdbligand=BZF:'>BZF</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Lysozyme Lysozyme], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.2.1.17 3.2.1.17] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=182L OCA].
 ==Reference==
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 [[Category: Lysozyme]]
 [[Category: Single protein]]
-[[Category: Matthews, B.W.]]
+[[Category: Matthews, B W.]]
 [[Category: Morton, A.]]
 [[Category: BZF]]
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 [[Category: hydrolase (o-glycosyl)]]
-''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Tue Nov 20 10:30:16 2007''
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