1w29

From Proteopedia

(Difference between revisions)
Jump to: navigation, search
Line 1: Line 1:
-
[[Image:1w29.gif|left|200px]]
+
{{Seed}}
 +
[[Image:1w29.png|left|200px]]
<!--
<!--
Line 9: Line 10:
{{STRUCTURE_1w29| PDB=1w29 | SCENE= }}
{{STRUCTURE_1w29| PDB=1w29 | SCENE= }}
-
'''LUMAZINE SYNTHASE FROM MYCOBACTERIUM TUBERCULOSIS BOUND TO 3-(1,3,7-TRIHYDRO-9-D-RIBITYL-2,6,8-PURINETRIONE-7-YL) BUTANE 1-PHOSPHATE'''
+
===LUMAZINE SYNTHASE FROM MYCOBACTERIUM TUBERCULOSIS BOUND TO 3-(1,3,7-TRIHYDRO-9-D-RIBITYL-2,6,8-PURINETRIONE-7-YL) BUTANE 1-PHOSPHATE===
-
==Overview==
+
<!--
-
The enzymes involved in the biosynthesis of riboflavin represent attractive targets for the development of drugs against bacterial pathogens, because the inhibitors of these enzymes are not likely to interfere with enzymes of the mammalian metabolism. Lumazine synthase catalyzes the penultimate step in the riboflavin biosynthesis pathway. A number of substituted purinetrione compounds represent a new class of highly specific inhibitors of lumazine synthase from Mycobacterium tuberculosis. To develop potent antibiotics for the treatment of tuberculosis, we have determined the structure of lumazine synthase from M. tuberculosis in complex with two purinetrione inhibitors and have studied binding via isothermal titration calorimetry. The structures were determined by molecular replacement using lumazine synthase from Saccharomyces cerevisiae as a search model and refined at 2 and 2.3 A resolution. The R-factors were 14.7 and 17.4%, respectively, and the R(free) values were 19.3 and 26.3%, respectively. The enzyme was found to be a pentamer consisting of five subunits related by 5-fold local symmetry. The comparison of the active site architecture with the active site of previously determined lumazine synthase structures reveals a largely conserved topology with the exception of residues Gln141 and Glu136, which participate in different charge-charge interactions in the core space of the active site. The impact of structural changes in the active site on the altered binding and catalytic properties of the enzyme is discussed. Isothermal titration calorimetry measurements indicate highly specific binding of the purinetrione inhibitors to the M. tuberculosis enzyme with dissociation constants in micromolar range.
+
The line below this paragraph, {{ABSTRACT_PUBMED_15723519}}, adds the Publication Abstract to the page
 +
(as it appears on PubMed at http://www.pubmed.gov), where 15723519 is the PubMed ID number.
 +
-->
 +
{{ABSTRACT_PUBMED_15723519}}
==About this Structure==
==About this Structure==
Line 33: Line 37:
[[Category: Crystal structure,mycobacterium tuberculosis,inhibitor binding,x-ray diffraction]]
[[Category: Crystal structure,mycobacterium tuberculosis,inhibitor binding,x-ray diffraction]]
[[Category: Transferase,riboflavin biosynthesis,lumazine synthase]]
[[Category: Transferase,riboflavin biosynthesis,lumazine synthase]]
-
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 13:03:03 2008''
+
 
 +
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Tue Jul 29 09:11:29 2008''

Revision as of 06:11, 29 July 2008

Image:1w29.png

Template:STRUCTURE 1w29

LUMAZINE SYNTHASE FROM MYCOBACTERIUM TUBERCULOSIS BOUND TO 3-(1,3,7-TRIHYDRO-9-D-RIBITYL-2,6,8-PURINETRIONE-7-YL) BUTANE 1-PHOSPHATE

Template:ABSTRACT PUBMED 15723519

About this Structure

1W29 is a Single protein structure of sequence from Mycobacterium tuberculosis. Full crystallographic information is available from OCA.

Reference

Crystal structure of lumazine synthase from Mycobacterium tuberculosis as a target for rational drug design: binding mode of a new class of purinetrione inhibitors., Morgunova E, Meining W, Illarionov B, Haase I, Jin G, Bacher A, Cushman M, Fischer M, Ladenstein R, Biochemistry. 2005 Mar 1;44(8):2746-58. PMID:15723519

Page seeded by OCA on Tue Jul 29 09:11:29 2008

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/1w29"
Personal tools