1ekx
From Proteopedia
(New page: 200px<br /><applet load="1ekx" size="450" color="white" frame="true" align="right" spinBox="true" caption="1ekx, resolution 1.95Å" /> '''THE ISOLATED, UNREGU...) |
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| - | [[Image:1ekx.jpg|left|200px]]<br /><applet load="1ekx" size=" | + | [[Image:1ekx.jpg|left|200px]]<br /><applet load="1ekx" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="1ekx, resolution 1.95Å" /> | caption="1ekx, resolution 1.95Å" /> | ||
'''THE ISOLATED, UNREGULATED CATALYTIC TRIMER OF ASPARTATE TRANSCARBAMOYLASE COMPLEXED WITH BISUBSTRATE ANALOG PALA (N-(PHOSPHONACETYL)-L-ASPARTATE)'''<br /> | '''THE ISOLATED, UNREGULATED CATALYTIC TRIMER OF ASPARTATE TRANSCARBAMOYLASE COMPLEXED WITH BISUBSTRATE ANALOG PALA (N-(PHOSPHONACETYL)-L-ASPARTATE)'''<br /> | ||
==Overview== | ==Overview== | ||
| - | A central problem in understanding enzyme regulation is to define the | + | A central problem in understanding enzyme regulation is to define the conformational states that account for allosteric changes in catalytic activity. For Escherichia coli aspartate transcarbamoylase (ATCase; EC) the active, relaxed (R state) holoenzyme is generally assumed to be represented by the crystal structure of the complex of the holoenzyme with the bisubstrate analog N-phosphonacetyl-L-aspartate (PALA). It is unclear, however, which conformational differences between the unliganded, inactive, taut (T state) holoenzyme and the PALA complex are attributable to localized effects of inhibitor binding as contrasted to the allosteric transition. To define the conformational changes in the isolated, nonallosteric C trimer resulting from the binding of PALA, we determined the 1.95-A resolution crystal structure of the C trimer-PALA complex. In contrast to the free C trimer, the PALA-bound trimer exhibits approximate threefold symmetry. Conformational changes in the C trimer upon PALA binding include ordering of two active site loops and closure of the hinge relating the N- and C-terminal domains. The C trimer-PALA structure closely resembles the liganded C subunits in the PALA-bound holoenzyme. This similarity suggests that the pronounced hinge closure and other changes promoted by PALA binding to the holoenzyme are stabilized by ligand binding. Consequently, the conformational changes attributable to the allosteric transition of the holoenzyme remain to be defined. |
==About this Structure== | ==About this Structure== | ||
| - | 1EKX 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 CA and PAL as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Aspartate_carbamoyltransferase Aspartate carbamoyltransferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.1.3.2 2.1.3.2] Full crystallographic information is available from [http:// | + | 1EKX 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=CA:'>CA</scene> and <scene name='pdbligand=PAL:'>PAL</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Aspartate_carbamoyltransferase Aspartate carbamoyltransferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.1.3.2 2.1.3.2] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1EKX OCA]. |
==Reference== | ==Reference== | ||
| - | Binding of bisubstrate analog promotes large structural changes in the unregulated catalytic trimer of aspartate transcarbamoylase: implications for allosteric regulation | + | Binding of bisubstrate analog promotes large structural changes in the unregulated catalytic trimer of aspartate transcarbamoylase: implications for allosteric regulation., Endrizzi JA, Beernink PT, Alber T, Schachman HK, Proc Natl Acad Sci U S A. 2000 May 9;97(10):5077-82. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=10805770 10805770] |
[[Category: Aspartate carbamoyltransferase]] | [[Category: Aspartate carbamoyltransferase]] | ||
[[Category: Escherichia coli]] | [[Category: Escherichia coli]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
[[Category: Alber, T.]] | [[Category: Alber, T.]] | ||
| - | [[Category: Beernink, P | + | [[Category: Beernink, P T.]] |
| - | [[Category: Endrizzi, J | + | [[Category: Endrizzi, J A.]] |
| - | [[Category: Schachman, H | + | [[Category: Schachman, H K.]] |
[[Category: CA]] | [[Category: CA]] | ||
[[Category: PAL]] | [[Category: PAL]] | ||
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[[Category: bisubstrate analog complex]] | [[Category: bisubstrate analog complex]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 12:28:57 2008'' |
Revision as of 10:29, 21 February 2008
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THE ISOLATED, UNREGULATED CATALYTIC TRIMER OF ASPARTATE TRANSCARBAMOYLASE COMPLEXED WITH BISUBSTRATE ANALOG PALA (N-(PHOSPHONACETYL)-L-ASPARTATE)
Overview
A central problem in understanding enzyme regulation is to define the conformational states that account for allosteric changes in catalytic activity. For Escherichia coli aspartate transcarbamoylase (ATCase; EC) the active, relaxed (R state) holoenzyme is generally assumed to be represented by the crystal structure of the complex of the holoenzyme with the bisubstrate analog N-phosphonacetyl-L-aspartate (PALA). It is unclear, however, which conformational differences between the unliganded, inactive, taut (T state) holoenzyme and the PALA complex are attributable to localized effects of inhibitor binding as contrasted to the allosteric transition. To define the conformational changes in the isolated, nonallosteric C trimer resulting from the binding of PALA, we determined the 1.95-A resolution crystal structure of the C trimer-PALA complex. In contrast to the free C trimer, the PALA-bound trimer exhibits approximate threefold symmetry. Conformational changes in the C trimer upon PALA binding include ordering of two active site loops and closure of the hinge relating the N- and C-terminal domains. The C trimer-PALA structure closely resembles the liganded C subunits in the PALA-bound holoenzyme. This similarity suggests that the pronounced hinge closure and other changes promoted by PALA binding to the holoenzyme are stabilized by ligand binding. Consequently, the conformational changes attributable to the allosteric transition of the holoenzyme remain to be defined.
About this Structure
1EKX is a Single protein structure of sequence from Escherichia coli with and as ligands. Active as Aspartate carbamoyltransferase, with EC number 2.1.3.2 Full crystallographic information is available from OCA.
Reference
Binding of bisubstrate analog promotes large structural changes in the unregulated catalytic trimer of aspartate transcarbamoylase: implications for allosteric regulation., Endrizzi JA, Beernink PT, Alber T, Schachman HK, Proc Natl Acad Sci U S A. 2000 May 9;97(10):5077-82. PMID:10805770
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