1z9w
From Proteopedia
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'''Tetrameric structure of apo-7,8-Dihydroneopterin Aldolase from Mycobacterium tuberculosis''' | '''Tetrameric structure of apo-7,8-Dihydroneopterin Aldolase from Mycobacterium tuberculosis''' | ||
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==About this Structure== | ==About this Structure== | ||
| - | 1Z9W is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Mycobacterium_tuberculosis Mycobacterium tuberculosis]. This structure supersedes the now removed PDB entry | + | 1Z9W is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Mycobacterium_tuberculosis Mycobacterium tuberculosis]. This structure supersedes the now removed PDB entry [http://oca.weizmann.ac.il/oca-bin/send-pdb?obs=1&id=1r7k 1r7k]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1Z9W OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Sawaya, M R.]] | [[Category: Sawaya, M R.]] | ||
[[Category: XMTB, Mycobacterium Tuberculosis Structural Proteomics Project.]] | [[Category: XMTB, Mycobacterium Tuberculosis Structural Proteomics Project.]] | ||
| - | [[Category: | + | [[Category: Folb]] |
| - | [[Category: | + | [[Category: Mycobacterium tuberculosis]] |
| - | [[Category: | + | [[Category: Mycobacterium tuberculosis structural proteomics project]] |
| - | [[Category: | + | [[Category: Protein structure initiative]] |
| - | [[Category: | + | [[Category: Psi]] |
| - | [[Category: | + | [[Category: Structural genomic]] |
| - | [[Category: | + | [[Category: Tb structural genomic]] |
| - | [[Category: | + | [[Category: Xmtb]] |
| - | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 17:22:05 2008'' | |
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | |
Revision as of 14:22, 3 May 2008
Tetrameric structure of apo-7,8-Dihydroneopterin Aldolase from Mycobacterium tuberculosis
Overview
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 Structure
1Z9W is a Single protein structure of sequence from Mycobacterium tuberculosis. This structure supersedes the now removed PDB entry 1r7k. Full crystallographic information is available from OCA.
Reference
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 17:22:05 2008
Categories: Dihydroneopterin aldolase | Mycobacterium tuberculosis | Single protein | Apostol, M I. | Eisenberg, D. | Goulding, C W. | Parseghian, A. | Philips, M. | Sawaya, M R. | XMTB, Mycobacterium Tuberculosis Structural Proteomics Project. | Folb | Mycobacterium tuberculosis structural proteomics project | Protein structure initiative | Psi | Structural genomic | Tb structural genomic | Xmtb
