1tal: Difference between revisions

Revision as of 16:11, 21 February 2008

ALPHA-LYTIC PROTEASE AT 120 K (SINGLE STRUCTURE MODEL)

OverviewOverview

Insight into the dynamic properties of alpha-lytic protease (alpha LP) has been obtained through the use of low-temperature X-ray crystallography and multiple-conformation refinement. Previous studies of alpha LP have shown that the residues around the active site are able to move significantly to accommodate substrates of different sizes. Here we show a link between the ability to accommodate ligands and the dynamics of the binding pocket. Although the structure of alpha LP at 120 K has B-factors with a uniformly low value of 4.8 A2 for the main chain, four regions stand out as having significantly higher B-factors. Because thermal motion should be suppressed at cryogenic temperatures, the high B-factors are interpreted as the result of trapped conformational substates. The active site residues that are perturbed during accommodation of different substrates are precisely those showing conformational substates, implying that substrate binding selects a subset of conformations from the ensemble of accessible states. To better characterize the precise nature of these substates, a protein model consisting of 16 structures has been refined and evaluated. The model reveals a number of features that could not be well-described by conventional B-factors: for example, 40% of the main-chain residue conformations are distributed asymmetrically or in discrete clusters. Furthermore, these data demonstrate an unexpected correlation between motions on either side of the binding pocket that we suggest is a consequence of "dynamic close packing." These results provide strong evidence for the role of protein dynamics in substrate binding and are consistent with the results of dynamic studies of ligand binding in myoglobin and ribonuclease A.

About this StructureAbout this Structure

1TAL is a Single protein structure of sequence from Lysobacter enzymogenes with and as ligands. Active as Alpha-lytic endopeptidase, with EC number 3.4.21.12 Full crystallographic information is available from OCA.

ReferenceReference

Conformational substates in enzyme mechanism: the 120 K structure of alpha-lytic protease at 1.5 A resolution., Rader SD, Agard DA, Protein Sci. 1997 Jul;6(7):1375-86. PMID:9232638

Page seeded by OCA on Thu Feb 21 15:11:41 2008

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OCA

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-[[Image:1tal.gif|left|200px]]<br /><applet load="1tal" size="450" color="white" frame="true" align="right" spinBox="true"
+[[Image:1tal.gif|left|200px]]<br /><applet load="1tal" size="350" color="white" frame="true" align="right" spinBox="true"
 caption="1tal, resolution 1.5&Aring;" />
 '''ALPHA-LYTIC PROTEASE AT 120 K (SINGLE STRUCTURE MODEL)'''<br />
 ==Overview==
-Insight into the dynamic properties of alpha-lytic protease (alpha LP) has, been obtained through the use of low-temperature X-ray crystallography and, multiple-conformation refinement. Previous studies of alpha LP have shown, that the residues around the active site are able to move significantly to, accommodate substrates of different sizes. Here we show a link between the, ability to accommodate ligands and the dynamics of the binding pocket., Although the structure of alpha LP at 120 K has B-factors with a uniformly, low value of 4.8 A2 for the main chain, four regions stand out as having, significantly higher B-factors. Because thermal motion should be, suppressed at cryogenic temperatures, the high B-factors are interpreted, as the result of trapped conformational substates. The active site, residues that are perturbed during accommodation of different substrates, are precisely those showing conformational substates, implying that, substrate binding selects a subset of conformations from the ensemble of, accessible states. To better characterize the precise nature of these, substates, a protein model consisting of 16 structures has been refined, and evaluated. The model reveals a number of features that could not be, well-described by conventional B-factors: for example, 40% of the, main-chain residue conformations are distributed asymmetrically or in, discrete clusters. Furthermore, these data demonstrate an unexpected, correlation between motions on either side of the binding pocket that we, suggest is a consequence of "dynamic close packing." These results provide, strong evidence for the role of protein dynamics in substrate binding and, are consistent with the results of dynamic studies of ligand binding in, myoglobin and ribonuclease A.
+Insight into the dynamic properties of alpha-lytic protease (alpha LP) has been obtained through the use of low-temperature X-ray crystallography and multiple-conformation refinement. Previous studies of alpha LP have shown that the residues around the active site are able to move significantly to accommodate substrates of different sizes. Here we show a link between the ability to accommodate ligands and the dynamics of the binding pocket. Although the structure of alpha LP at 120 K has B-factors with a uniformly low value of 4.8 A2 for the main chain, four regions stand out as having significantly higher B-factors. Because thermal motion should be suppressed at cryogenic temperatures, the high B-factors are interpreted as the result of trapped conformational substates. The active site residues that are perturbed during accommodation of different substrates are precisely those showing conformational substates, implying that substrate binding selects a subset of conformations from the ensemble of accessible states. To better characterize the precise nature of these substates, a protein model consisting of 16 structures has been refined and evaluated. The model reveals a number of features that could not be well-described by conventional B-factors: for example, 40% of the main-chain residue conformations are distributed asymmetrically or in discrete clusters. Furthermore, these data demonstrate an unexpected correlation between motions on either side of the binding pocket that we suggest is a consequence of "dynamic close packing." These results provide strong evidence for the role of protein dynamics in substrate binding and are consistent with the results of dynamic studies of ligand binding in myoglobin and ribonuclease A.
 ==About this Structure==
-TAL is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Lysobacter_enzymogenes Lysobacter enzymogenes] with SO4 and TAM as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Alpha-lytic_endopeptidase Alpha-lytic endopeptidase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.21.12 3.4.21.12] Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1TAL OCA].
+TAL is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Lysobacter_enzymogenes Lysobacter enzymogenes] with <scene name='pdbligand=SO4:'>SO4</scene> and <scene name='pdbligand=TAM:'>TAM</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Alpha-lytic_endopeptidase Alpha-lytic endopeptidase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.21.12 3.4.21.12] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1TAL OCA].
 ==Reference==
@@ Line 14: / Line 14: @@
 [[Category: Lysobacter enzymogenes]]
 [[Category: Single protein]]
-[[Category: Agard, D.A.]]
+[[Category: Agard, D A.]]
-[[Category: Rader, S.D.]]
+[[Category: Rader, S D.]]
 [[Category: SO4]]
 [[Category: TAM]]
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 [[Category: serine proteinase]]
-''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Wed Nov 21 03:07:12 2007''
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 15:11:41 2008''