2a7x
From Proteopedia
(New page: 200px<br /><applet load="2a7x" size="450" color="white" frame="true" align="right" spinBox="true" caption="2a7x, resolution 1.70Å" /> '''Crystal Structure of...) |
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| - | [[Image:2a7x.gif|left|200px]]<br /><applet load="2a7x" size=" | + | [[Image:2a7x.gif|left|200px]]<br /><applet load="2a7x" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="2a7x, resolution 1.70Å" /> | caption="2a7x, resolution 1.70Å" /> | ||
'''Crystal Structure of A Pantothenate synthetase complexed with AMP'''<br /> | '''Crystal Structure of A Pantothenate synthetase complexed with AMP'''<br /> | ||
==Overview== | ==Overview== | ||
| - | Pantothenate synthetase (PS) from Mycobacterium tuberculosis represents a | + | Pantothenate synthetase (PS) from Mycobacterium tuberculosis represents a potential target for antituberculosis drugs. PS catalyzes the ATP-dependent condensation of pantoate and beta-alanine to form pantothenate. Previously, we determined the crystal structure of PS from M. tuberculosis and its complexes with AMPCPP, pantoate, and pantoyl adenylate. Here, we describe the crystal structure of this enzyme complexed with AMP and its last substrate, beta-alanine, and show that the phosphate group of AMP serves as an anchor for the binding of beta-alanine. This structure confirms that binding of beta-alanine in the active site cavity can occur only after formation of the pantoyl adenylate intermediate. A new crystal form was also obtained; it displays the flexible wall of the active site cavity in a conformation incapable of binding pantoate. Soaking of this crystal form with ATP and pantoate gives a fully occupied complex of PS with ATP. Crystal structures of these complexes with substrates, the reaction intermediate, and the reaction product AMP provide a step-by-step view of the PS-catalyzed reaction. A detailed reaction mechanism and its implications for inhibitor design are discussed. |
==About this Structure== | ==About this Structure== | ||
| - | 2A7X is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Mycobacterium_tuberculosis Mycobacterium tuberculosis] with SO4, AMP and GOL as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Pantoate--beta-alanine_ligase Pantoate--beta-alanine ligase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=6.3.2.1 6.3.2.1] Full crystallographic information is available from [http:// | + | 2A7X is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Mycobacterium_tuberculosis Mycobacterium tuberculosis] with <scene name='pdbligand=SO4:'>SO4</scene>, <scene name='pdbligand=AMP:'>AMP</scene> and <scene name='pdbligand=GOL:'>GOL</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Pantoate--beta-alanine_ligase Pantoate--beta-alanine ligase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=6.3.2.1 6.3.2.1] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2A7X OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Single protein]] | [[Category: Single protein]] | ||
[[Category: Eisenberg, D.]] | [[Category: Eisenberg, D.]] | ||
| - | [[Category: TBSGC, TB | + | [[Category: TBSGC, TB Structural Genomics Consortium.]] |
[[Category: Wang, S.]] | [[Category: Wang, S.]] | ||
[[Category: AMP]] | [[Category: AMP]] | ||
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[[Category: tbsgc]] | [[Category: tbsgc]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 16:24:29 2008'' |
Revision as of 14:24, 21 February 2008
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Crystal Structure of A Pantothenate synthetase complexed with AMP
Overview
Pantothenate synthetase (PS) from Mycobacterium tuberculosis represents a potential target for antituberculosis drugs. PS catalyzes the ATP-dependent condensation of pantoate and beta-alanine to form pantothenate. Previously, we determined the crystal structure of PS from M. tuberculosis and its complexes with AMPCPP, pantoate, and pantoyl adenylate. Here, we describe the crystal structure of this enzyme complexed with AMP and its last substrate, beta-alanine, and show that the phosphate group of AMP serves as an anchor for the binding of beta-alanine. This structure confirms that binding of beta-alanine in the active site cavity can occur only after formation of the pantoyl adenylate intermediate. A new crystal form was also obtained; it displays the flexible wall of the active site cavity in a conformation incapable of binding pantoate. Soaking of this crystal form with ATP and pantoate gives a fully occupied complex of PS with ATP. Crystal structures of these complexes with substrates, the reaction intermediate, and the reaction product AMP provide a step-by-step view of the PS-catalyzed reaction. A detailed reaction mechanism and its implications for inhibitor design are discussed.
About this Structure
2A7X is a Single protein structure of sequence from Mycobacterium tuberculosis with , and as ligands. Active as Pantoate--beta-alanine ligase, with EC number 6.3.2.1 Full crystallographic information is available from OCA.
Reference
Crystal structure of the pantothenate synthetase from Mycobacterium tuberculosis, snapshots of the enzyme in action., Wang S, Eisenberg D, Biochemistry. 2006 Feb 14;45(6):1554-61. PMID:16460002
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Categories: Mycobacterium tuberculosis | Pantoate--beta-alanine ligase | Single protein | Eisenberg, D. | TBSGC, TB Structural Genomics Consortium. | Wang, S. | AMP | GOL | SO4 | Protein structure initiative | Protein-product inhibitor complex | Psi | Structural genomics | Tb structural genomics consortium | Tbsgc
