2fb3: Difference between revisions

Revision as of 03:40, 4 May 2008

Structure of MoaA in complex with 5'-GTP

OverviewOverview

The first step in molybdenum cofactor biosynthesis, the conversion of 5'-GTP to precursor Z, an oxygen-sensitive tetrahydropyranopterin is catalyzed by the S-adenosylmethionine (SAM)-dependent enzyme MoaA and the accessory protein MoaC. This reaction involves the radical-initiated intramolecular rearrangement of the guanine C8 atom. MoaA harbors an N-terminal [4Fe-4S] cluster, which is involved in the reductive cleavage of SAM and generates a 5'-deoxyadenosyl radical (5'-dA*), and a C-terminal [4Fe-4S] cluster presumably involved in substrate binding and/or activation. Biochemical studies identified residues involved in 5'-GTP binding and the determinants of nucleotide specificity. The crystal structure of MoaA in complex with 5'-GTP confirms the biochemical data and provides valuable insights into the subsequent radical reaction. MoaA binds 5'-GTP with high affinity and interacts through its C-terminal [4Fe-4S] cluster with the guanine N1 and N2 atoms, in a yet uncharacterized binding mode. The tightly anchored triphosphate moiety prevents the escape of radical intermediates. This structure also visualizes the L-Met and 5'-dA cleavage products of SAM. Rotation of the 5'-dA ribose and/or conformational changes of the guanosine are proposed to bring the 5'-deoxyadenosyl radical into close proximity of either the ribose C2' and C3' or the guanine C8 carbon atoms leading to hydrogen abstraction.

About this StructureAbout this Structure

2FB3 is a Single protein structure of sequence from Staphylococcus aureus. Full crystallographic information is available from OCA.

ReferenceReference

Binding of 5'-GTP to the C-terminal FeS cluster of the radical S-adenosylmethionine enzyme MoaA provides insights into its mechanism., Hanzelmann P, Schindelin H, Proc Natl Acad Sci U S A. 2006 May 2;103(18):6829-34. Epub 2006 Apr 21. PMID:16632608 Page seeded by OCA on Sun May 4 03:40:51 2008

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OCA

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 [[Image:2fb3.gif|left|200px]]
- {{Structure
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-|GENE= MoaA ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=1280 Staphylococcus aureus])
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-|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2fb3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2fb3 OCA], [http://www.ebi.ac.uk/pdbsum/2fb3 PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=2fb3 RCSB]</span>
-}}
 '''Structure of MoaA in complex with 5'-GTP'''
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 [[Category: 5'-deoxyadenosine]]
 [[Category: 5'-gtp]]
-[[Category: [4fe-4s] cluster]]
+[[Category: S-adenosylmethionine]]
-[[Category: s-adenosylmethionine]]
+[[Category: Tim barrel]]
-[[Category: tim barrel]]
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May  4 03:40:51 2008''
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 03:00:18 2008''