2c9d: Difference between revisions

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Revision as of 17:12, 20 March 2008

File:2c9d.jpg

, resolution 2.80Å

Sites:

Ligands:

, and

Activity:

Riboflavin synthase, with EC number 2.5.1.9

Coordinates:

save as pdb, mmCIF, xml

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

OverviewOverview

Recently published genomic investigations of the human pathogen Mycobacterium tuberculosis have revealed that genes coding the proteins involved in riboflavin biosynthesis are essential for the growth of the organism. Because the enzymes involved in cofactor biosynthesis pathways are not present in humans, they appear to be promising candidates for the development of therapeutic drugs. The substituted purinetrione compounds have demonstrated high affinity and specificity to lumazine synthase, which catalyzes the penultimate step of riboflavin biosynthesis in bacteria and plants. The structure of M. tuberculosis lumazine synthase in complex with five different inhibitor compounds is presented, together with studies of the binding reactions by isothermal titration calorimetry. The inhibitors showed the association constants in the micromolar range. The analysis of the structures demonstrated the specific features of the binding of different inhibitors. The comparison of the structures and binding modes of five different inhibitors allows us to propose the ribitylpurinetrione compounds with C4-C5 alkylphosphate chains as most promising leads for further development of therapeutic drugs against M. tuberculosis.

About this StructureAbout this Structure

2C9D is a Single protein structure of sequence from Mycobacterium tuberculosis. Full crystallographic information is available from OCA.

ReferenceReference

Structural and thermodynamic insights into the binding mode of five novel inhibitors of lumazine synthase from Mycobacterium tuberculosis., Morgunova E, Illarionov B, Sambaiah T, Haase I, Bacher A, Cushman M, Fischer M, Ladenstein R, FEBS J. 2006 Oct;273(20):4790-804. Epub 2006 Sep 19. PMID:16984393

Page seeded by OCA on Thu Mar 20 16:12:44 2008

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OCA

@@ Line 1: / Line 1: @@
-[[Image:2c9d.jpg|left|200px]]<br /><applet load="2c9d" size="350" color="white" frame="true" align="right" spinBox="true"
+[[Image:2c9d.jpg|left|200px]]
-caption="2c9d, resolution 2.80&Aring;" />
-'''LUMAZINE SYNTHASE FROM MYCOBACTERIUM TUBERCULOSIS BOUND TO 3-(1,3,7-TRIHYDRO-9-D-RIBITYL-2,6,8-PURINETRIONE-7-YL) HEXANE 1-PHOSPHATE'''<br />
+ {{Structure
+|PDB= 2c9d |SIZE=350|CAPTION= <scene name='initialview01'>2c9d</scene>, resolution 2.80&Aring;
+|SITE= <scene name='pdbsite=AC1:Mpd+Binding+Site+For+Chain+J'>AC1</scene>
+|LIGAND= <scene name='pdbligand=K:POTASSIUM+ION'>K</scene>, <scene name='pdbligand=PHR:3-(1,3,7-TRIHYDRO-9-D-RIBITYL-2,6,8-PURINETRIONE-7-YL+)+HEXANE+1-PHOSPHATE'>PHR</scene> and <scene name='pdbligand=MPD:(4S)-2-METHYL-2,4-PENTANEDIOL'>MPD</scene>
+|ACTIVITY= [http://en.wikipedia.org/wiki/Riboflavin_synthase Riboflavin synthase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.5.1.9 2.5.1.9]
+|GENE=
+}}
+'''LUMAZINE SYNTHASE FROM MYCOBACTERIUM TUBERCULOSIS BOUND TO 3-(1,3,7-TRIHYDRO-9-D-RIBITYL-2,6,8-PURINETRIONE-7-YL) HEXANE 1-PHOSPHATE'''
 ==Overview==
@@ Line 7: / Line 16: @@
 ==About this Structure==
-C9D 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=K:'>K</scene>, <scene name='pdbligand=PHR:'>PHR</scene> and <scene name='pdbligand=MPD:'>MPD</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Riboflavin_synthase Riboflavin synthase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.5.1.9 2.5.1.9] Known structural/functional Site: <scene name='pdbsite=AC1:Mpd+Binding+Site+For+Chain+J'>AC1</scene>. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2C9D OCA].
+C9D is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Mycobacterium_tuberculosis Mycobacterium tuberculosis]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2C9D OCA].
 ==Reference==
-Structural and thermodynamic insights into the binding mode of five novel inhibitors of lumazine synthase from Mycobacterium tuberculosis., Morgunova E, Illarionov B, Sambaiah T, Haase I, Bacher A, Cushman M, Fischer M, Ladenstein R, FEBS J. 2006 Oct;273(20):4790-804. Epub 2006 Sep 19. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=16984393 16984393]
+Structural and thermodynamic insights into the binding mode of five novel inhibitors of lumazine synthase from Mycobacterium tuberculosis., Morgunova E, Illarionov B, Sambaiah T, Haase I, Bacher A, Cushman M, Fischer M, Ladenstein R, FEBS J. 2006 Oct;273(20):4790-804. Epub 2006 Sep 19. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/16984393 16984393]
 [[Category: Mycobacterium tuberculosis]]
 [[Category: Riboflavin synthase]]
@@ Line 31: / Line 40: @@
 [[Category: transferase]]
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 16:46:18 2008''
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 16:12:44 2008''