1g0r: Difference between revisions
New page: left|200px<br /><applet load="1g0r" size="450" color="white" frame="true" align="right" spinBox="true" caption="1g0r, resolution 1.87Å" /> '''THE STRUCTURAL BASIS... |
No edit summary |
||
| Line 1: | Line 1: | ||
[[Image:1g0r.jpg|left|200px]]<br /><applet load="1g0r" size=" | [[Image:1g0r.jpg|left|200px]]<br /><applet load="1g0r" size="350" color="white" frame="true" align="right" spinBox="true" | ||
caption="1g0r, resolution 1.87Å" /> | caption="1g0r, resolution 1.87Å" /> | ||
'''THE STRUCTURAL BASIS OF THE CATALYTIC MECHANISM AND REGULATION OF GLUCOSE-1-PHOSPHATE THYMIDYLYLTRANSFERASE (RMLA). THYMIDINE/GLUCOSE-1-PHOSPHATE COMPLEX.'''<br /> | '''THE STRUCTURAL BASIS OF THE CATALYTIC MECHANISM AND REGULATION OF GLUCOSE-1-PHOSPHATE THYMIDYLYLTRANSFERASE (RMLA). THYMIDINE/GLUCOSE-1-PHOSPHATE 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== | ||
1G0R 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 G1P, SO4 and THM as [http://en.wikipedia.org/wiki/ligands ligands]. 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:// | 1G0R 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=G1P:'>G1P</scene>, <scene name='pdbligand=SO4:'>SO4</scene> and <scene name='pdbligand=THM:'>THM</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. 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=1G0R OCA]. | ||
==Reference== | ==Reference== | ||
| Line 16: | Line 16: | ||
[[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: G1P]] | [[Category: G1P]] | ||
[[Category: SO4]] | [[Category: SO4]] | ||
| Line 27: | Line 27: | ||
[[Category: thymidylyltransferase]] | [[Category: thymidylyltransferase]] | ||
''Page seeded by [http:// | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 12:44:45 2008'' | ||
Revision as of 13:44, 21 February 2008
|
THE STRUCTURAL BASIS OF THE CATALYTIC MECHANISM AND REGULATION OF GLUCOSE-1-PHOSPHATE THYMIDYLYLTRANSFERASE (RMLA). THYMIDINE/GLUCOSE-1-PHOSPHATE COMPLEX.
OverviewOverview
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 StructureAbout this Structure
1G0R is a Single protein structure of sequence from Pseudomonas aeruginosa with , and as ligands. Active as Glucose-1-phosphate thymidylyltransferase, with EC number 2.7.7.24 Full crystallographic information is available from OCA.
ReferenceReference
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
Page seeded by OCA on Thu Feb 21 12:44:45 2008