1g2v
From Proteopedia
(New page: 200px<br /><applet load="1g2v" size="450" color="white" frame="true" align="right" spinBox="true" caption="1g2v, resolution 2.60Å" /> '''THE STRUCTURAL BASIS...) |
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| - | [[Image:1g2v.gif|left|200px]]<br /><applet load="1g2v" size=" | + | [[Image:1g2v.gif|left|200px]]<br /><applet load="1g2v" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="1g2v, resolution 2.60Å" /> | caption="1g2v, resolution 2.60Å" /> | ||
'''THE STRUCTURAL BASIS OF THE CATALYTIC MECHANISM AND REGULATION OF GLUCOSE-1-PHOSPHATE THYMIDYLYLTRANSFERASE (RMLA). TTP COMPLEX.'''<br /> | '''THE STRUCTURAL BASIS OF THE CATALYTIC MECHANISM AND REGULATION OF GLUCOSE-1-PHOSPHATE THYMIDYLYLTRANSFERASE (RMLA). TTP COMPLEX.'''<br /> | ||
==Overview== | ==Overview== | ||
| - | The synthesis of deoxy-thymidine di-phosphate (dTDP)-L-rhamnose, an | + | The synthesis of deoxy-thymidine di-phosphate (dTDP)-L-rhamnose, an important component of the cell wall of many microorganisms, is a target for therapeutic intervention. The first enzyme in the dTDP-L-rhamnose biosynthetic pathway is glucose-1-phosphate thymidylyltransferase (RmlA). RmlA is inhibited by dTDP-L-rhamnose thereby regulating L-rhamnose production in bacteria. The structure of Pseudomonas aeruginosa RmlA has been solved to 1.66 A resolution. RmlA is a homotetramer, with the monomer consisting of three functional subdomains. The sugar binding and dimerization subdomains are unique to RmlA-like enzymes. The sequence of the core subdomain is found not only in sugar nucleotidyltransferases but also in other nucleotidyltransferases. The structures of five distinct enzyme substrate- product complexes reveal the enzyme mechanism that involves precise positioning of the nucleophile and activation of the electrophile. All the key residues are within the core subdomain, suggesting that the basic mechanism is found in many nucleotidyltransferases. The dTDP-L-rhamnose complex identifies how the protein is controlled by its natural inhibitor. This work provides a platform for the design of novel drugs against pathogenic bacteria. |
==About this Structure== | ==About this Structure== | ||
| - | 1G2V is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Pseudomonas_aeruginosa Pseudomonas aeruginosa] with TTP as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [http://en.wikipedia.org/wiki/Glucose-1-phosphate_thymidylyltransferase Glucose-1-phosphate thymidylyltransferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.7.24 2.7.7.24] Full crystallographic information is available from [http:// | + | 1G2V is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Pseudomonas_aeruginosa Pseudomonas aeruginosa] with <scene name='pdbligand=TTP:'>TTP</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [http://en.wikipedia.org/wiki/Glucose-1-phosphate_thymidylyltransferase Glucose-1-phosphate thymidylyltransferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.7.24 2.7.7.24] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1G2V OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Asuncion, M.]] | [[Category: Asuncion, M.]] | ||
[[Category: Blankenfeldt, W.]] | [[Category: Blankenfeldt, W.]] | ||
| - | [[Category: Lam, J | + | [[Category: Lam, J S.]] |
| - | [[Category: Naismith, J | + | [[Category: Naismith, J H.]] |
[[Category: TTP]] | [[Category: TTP]] | ||
[[Category: allostery]] | [[Category: allostery]] | ||
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[[Category: thymidylyltransferase]] | [[Category: thymidylyltransferase]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 12:45:30 2008'' |
Revision as of 10:45, 21 February 2008
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THE STRUCTURAL BASIS OF THE CATALYTIC MECHANISM AND REGULATION OF GLUCOSE-1-PHOSPHATE THYMIDYLYLTRANSFERASE (RMLA). TTP COMPLEX.
Overview
The synthesis of deoxy-thymidine di-phosphate (dTDP)-L-rhamnose, an important component of the cell wall of many microorganisms, is a target for therapeutic intervention. The first enzyme in the dTDP-L-rhamnose biosynthetic pathway is glucose-1-phosphate thymidylyltransferase (RmlA). RmlA is inhibited by dTDP-L-rhamnose thereby regulating L-rhamnose production in bacteria. The structure of Pseudomonas aeruginosa RmlA has been solved to 1.66 A resolution. RmlA is a homotetramer, with the monomer consisting of three functional subdomains. The sugar binding and dimerization subdomains are unique to RmlA-like enzymes. The sequence of the core subdomain is found not only in sugar nucleotidyltransferases but also in other nucleotidyltransferases. The structures of five distinct enzyme substrate- product complexes reveal the enzyme mechanism that involves precise positioning of the nucleophile and activation of the electrophile. All the key residues are within the core subdomain, suggesting that the basic mechanism is found in many nucleotidyltransferases. The dTDP-L-rhamnose complex identifies how the protein is controlled by its natural inhibitor. This work provides a platform for the design of novel drugs against pathogenic bacteria.
About this Structure
1G2V is a Single protein structure of sequence from Pseudomonas aeruginosa with as ligand. Active as Glucose-1-phosphate thymidylyltransferase, with EC number 2.7.7.24 Full crystallographic information is available from OCA.
Reference
The structural basis of the catalytic mechanism and regulation of glucose-1-phosphate thymidylyltransferase (RmlA)., Blankenfeldt W, Asuncion M, Lam JS, Naismith JH, EMBO J. 2000 Dec 15;19(24):6652-63. PMID:11118200
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