2fb2
From Proteopedia
(New page: 200px<br /><applet load="2fb2" size="450" color="white" frame="true" align="right" spinBox="true" caption="2fb2, resolution 2.25Å" /> '''Structure of the Moa...) |
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| - | [[Image:2fb2.gif|left|200px]]<br /><applet load="2fb2" size=" | + | [[Image:2fb2.gif|left|200px]]<br /><applet load="2fb2" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="2fb2, resolution 2.25Å" /> | caption="2fb2, resolution 2.25Å" /> | ||
'''Structure of the MoaA Arg17/266/268/Ala triple mutant'''<br /> | '''Structure of the MoaA Arg17/266/268/Ala triple mutant'''<br /> | ||
==Overview== | ==Overview== | ||
| - | The first step in molybdenum cofactor biosynthesis, the conversion of | + | 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 Structure== | ==About this Structure== | ||
| - | 2FB2 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Staphylococcus_aureus Staphylococcus aureus] with SO4, SAM and SF4 as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http:// | + | 2FB2 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Staphylococcus_aureus Staphylococcus aureus] with <scene name='pdbligand=SO4:'>SO4</scene>, <scene name='pdbligand=SAM:'>SAM</scene> and <scene name='pdbligand=SF4:'>SF4</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2FB2 OCA]. |
==Reference== | ==Reference== | ||
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[[Category: tim barrel]] | [[Category: tim barrel]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 17:19:36 2008'' |
Revision as of 15:19, 21 February 2008
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Structure of the MoaA Arg17/266/268/Ala triple mutant
Overview
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 Structure
2FB2 is a Single protein structure of sequence from Staphylococcus aureus with , and as ligands. Full crystallographic information is available from OCA.
Reference
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[[Category: [4fe-4s] clusters]]
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