1nbu: Difference between revisions
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==7,8-Dihydroneopterin Aldolase Complexed with Product From Mycobacterium Tuberculosis== | ==7,8-Dihydroneopterin Aldolase Complexed with Product From Mycobacterium Tuberculosis== | ||
<StructureSection load='1nbu' size='340' side='right' caption='[[1nbu]], [[Resolution|resolution]] 1.60Å' scene=''> | <StructureSection load='1nbu' size='340' side='right'caption='[[1nbu]], [[Resolution|resolution]] 1.60Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[1nbu]] is a 8 chain structure with sequence from [ | <table><tr><td colspan='2'>[[1nbu]] is a 8 chain structure with sequence from [https://en.wikipedia.org/wiki/Mycobacterium_tuberculosis Mycobacterium tuberculosis]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1NBU OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1NBU FirstGlance]. <br> | ||
</td></tr><tr id=' | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.6Å</td></tr> | ||
<tr id=' | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=PH2:2-AMINO-6-HYDROXYMETHYL-7,8-DIHYDRO-3H-PTERIDIN-4-ONE'>PH2</scene></td></tr> | ||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1nbu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1nbu OCA], [https://pdbe.org/1nbu PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1nbu RCSB], [https://www.ebi.ac.uk/pdbsum/1nbu PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1nbu ProSAT]</span></td></tr> | |||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | |||
</table> | </table> | ||
== Function == | == Function == | ||
[ | [https://www.uniprot.org/uniprot/FOLB_MYCTU FOLB_MYCTU] Catalyzes the conversion of 7,8-dihydroneopterin to 6-hydroxymethyl-7,8-dihydropterin (By similarity). | ||
== Evolutionary Conservation == | == Evolutionary Conservation == | ||
[[Image:Consurf_key_small.gif|200px|right]] | [[Image:Consurf_key_small.gif|200px|right]] | ||
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__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: | [[Category: Large Structures]] | ||
[[Category: Apostol | [[Category: Mycobacterium tuberculosis]] | ||
[[Category: Eisenberg | [[Category: Apostol MI]] | ||
[[Category: Goulding | [[Category: Eisenberg D]] | ||
[[Category: Parseghian | [[Category: Goulding CW]] | ||
[[Category: Phillips | [[Category: Parseghian A]] | ||
[[Category: Sawaya | [[Category: Phillips M]] | ||
[[Category: Sawaya MR]] | |||
Latest revision as of 12:18, 16 August 2023
7,8-Dihydroneopterin Aldolase Complexed with Product From Mycobacterium Tuberculosis7,8-Dihydroneopterin Aldolase Complexed with Product From Mycobacterium Tuberculosis
Structural highlights
FunctionFOLB_MYCTU Catalyzes the conversion of 7,8-dihydroneopterin to 6-hydroxymethyl-7,8-dihydropterin (By similarity). Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedFolate 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. 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[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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