1nbu: Difference between revisions

Revision as of 02:20, 3 May 2008

7,8-Dihydroneopterin Aldolase Complexed with Product From Mycobacterium Tuberculosis

OverviewOverview

Folate derivatives are essential cofactors in the biosynthesis of purines, pyrimidines and amino acids across all forms of life. Mammals uptake folate from their diets, whereas most bacteria must synthesize folate de novo. Therefore, the enzymes in the folate biosynthetic pathway are attractive drug targets against bacterial pathogens such as Mycobacterium tuberculosis, the cause of the world's most deadly infectious disease, tuberculosis (TB). M.tuberculosis 7,8-dihydroneopterin aldolase (Mtb FolB, DHNA) is the second enzyme in the folate biosynthetic pathway, which catalyzes the conversion of 7,8-dihydroneopterin to 6-hydroxymethyl-7,8-dihydropterin and glycoaldehyde. The 1.6A X-ray crystal structure of Mtb FolB complexed with its product, 6-hydroxymethyl-7,8-dihydropterin, reveals an octameric assembly similar to that seen in crystal structures of other FolB homologs. However, the 2.5A crystal structure of unliganded Mtb FolB reveals a novel tetrameric oligomerization state, with only partially formed active sites. A substrate induced conformational change appears to be necessary to convert the inactive tetramer to the active octamer. Ultracentrifugation confirmed that in solution unliganded Mtb FolB is mainly tetrameric and upon addition of substrate FolB is predominantly octameric. Kinetic analysis of substrate binding gives a Hill coefficient of 2.0, indicating positive cooperativity. We hypothesize that Mtb FolB displays cooperativity in substrate binding to regulate the cellular concentration of 7,8-dihydroneopterin, so that it may function not only as a precursor to folate but also as an antioxidant for the survival of M.tuberculosis against host defenses.

About this StructureAbout this Structure

1NBU is a Protein complex structure of sequences from Mycobacterium tuberculosis. Full crystallographic information is available from OCA.

ReferenceReference

Regulation by oligomerization in a mycobacterial folate biosynthetic enzyme., Goulding CW, Apostol MI, Sawaya MR, Phillips M, Parseghian A, Eisenberg D, J Mol Biol. 2005 May 27;349(1):61-72. Epub 2005 Apr 2. PMID:15876368 Page seeded by OCA on Sat May 3 02:20:34 2008

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OCA

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 [[Image:1nbu.gif|left|200px]]
- {{Structure
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+The line below this paragraph, containing "STRUCTURE_1nbu", creates the "Structure Box" on the page.
-|SITE=
+You may change the PDB parameter (which sets the PDB file loaded into the applet)
-|LIGAND= <scene name='pdbligand=PH2:2-AMINO-6-HYDROXYMETHYL-7,8-DIHYDRO-3H-PTERIDIN-4-ONE'>PH2</scene>
+or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
-|ACTIVITY= <span class='plainlinks'>[http://en.wikipedia.org/wiki/Dihydroneopterin_aldolase Dihydroneopterin aldolase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=4.1.2.25 4.1.2.25] </span>
+or leave the SCENE parameter empty for the default display.
-|GENE= FOLB OR RV3607C OR MT3712.1 OR MTCY07H7B.15 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=1773 Mycobacterium tuberculosis])
+-->
-|DOMAIN=<span class='plainlinks'>[http://www.ncbi.nlm.nih.gov/Structure/cdd/cddsrv.cgi?uid=cd00534 DHNA_DHNTPE]</span>
+{{STRUCTURE_1nbu|  PDB=1nbu  |  SCENE=  }}
-|RELATEDENTRY=
-|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1nbu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1nbu OCA], [http://www.ebi.ac.uk/pdbsum/1nbu PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1nbu RCSB]</span>
-}}
 '''7,8-Dihydroneopterin Aldolase Complexed with Product From Mycobacterium Tuberculosis'''
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 [[Category: Sawaya, M R.]]
 [[Category: TBSGC, TB Structural Genomics Consortium.]]
-[[Category: anti-parallel]]
+[[Category: Anti-parallel]]
-[[Category: beta-sheet]]
+[[Category: Beta-sheet]]
-[[Category: protein structure initiative]]
+[[Category: Protein structure initiative]]
-[[Category: psi]]
+[[Category: Psi]]
-[[Category: structural genomic]]
+[[Category: Structural genomic]]
-[[Category: tb structural genomics consortium]]
+[[Category: Tb structural genomics consortium]]
-[[Category: tbsgc]]
+[[Category: Tbsgc]]
-[[Category: two alpha helice]]
+[[Category: Two alpha helice]]
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May  3 02:20:34 2008''
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Mar 30 22:28:12 2008''