Adenosine dimethyltransferase: Difference between revisions

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Among methyltransferases, KsgA and the reaction it catalyzes are conserved throughout evolution. However, the specifics of substrate recognition by the enzyme remain unknown. Here we report structures of <scene name='59/597431/Cv/3'>Aquifex aeolicus KsgA, in its ligand-free form, in complex with RNA, and in complex with both RNA and S-adenosylhomocysteine</scene> (SAH, reaction product of cofactor S-adenosylmethionine), revealing critical structural information on KsgA-RNA and KsgA-SAH interactions. Moreover, the structures show how conformational changes that occur upon RNA binding create the cofactor-binding site. There are nine conserved functional motifs (motifs I-VIII and X) in KsgA. Prior to RNA binding, motifs I and VIII are flexible, each exhibiting two distinct conformations. Upon RNA binding, the two motifs become stabilized in one of these conformations, which is compatible with the binding of SAH. Motif X, which is also stabilized upon RNA binding, is directly involved in the binding of SAH.<ref>PMID:19278652</ref>
Among methyltransferases, KsgA and the reaction it catalyzes are conserved throughout evolution. However, the specifics of substrate recognition by the enzyme remain unknown. Here we report structures of <scene name='59/597431/Cv/3'>Aquifex aeolicus KsgA, in its ligand-free form, in complex with RNA, and in complex with both RNA and S-adenosylhomocysteine</scene> (SAH, reaction product of cofactor S-adenosylmethionine), revealing critical structural information on KsgA-RNA and KsgA-SAH interactions. Moreover, the structures show how conformational changes that occur upon RNA binding create the cofactor-binding site. There are nine conserved functional motifs (motifs I-VIII and X) in KsgA. Prior to RNA binding, motifs I and VIII are flexible, each exhibiting two distinct conformations. Upon RNA binding, the two motifs become stabilized in one of these conformations, which is compatible with the binding of SAH. Motif X, which is also stabilized upon RNA binding, is directly involved in the binding of SAH.<ref>PMID:19278652</ref>
==3D structures of adenosine dimethyltransferase==
[[Adenosine dimethyltransferase 3D structures]]


</StructureSection>
</StructureSection>
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**[[3uzu]] – KsgA – ''Burkholderia pseudomallei''<br />
**[[3uzu]] – KsgA – ''Burkholderia pseudomallei''<br />
**[[4jxj]] – KsgA – ''Rickettsia bellii''<br />
**[[4jxj]] – KsgA – ''Rickettsia bellii''<br />
**[[6ifs]], [[6ifv]], [[6ifw]], [[6ifx]] – BsKsgA – ''Bacillus subtilis''<br />


*Adenosine dimethyltransferase complex
*Adenosine dimethyltransferase complex
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**[[3r9x]] – AaKsgA + GDPNP + RNA + GTPase<br />
**[[3r9x]] – AaKsgA + GDPNP + RNA + GTPase<br />
**[[4adv]] – EcKsgA + 30S ribosomal subunit – Cryo-EM<br />
**[[4adv]] – EcKsgA + 30S ribosomal subunit – Cryo-EM<br />
**[[4lf4]], [[4lf5]], [[4lf6]], [[4lf7]], [[4lf8]], [[4lf9]], [[4lfa]], [[4lfb]], [[4lfc]] – TtKsgA + 30S ribosomal subunit <br />
**[[6ift]] – SbKsgA + SAM<br />
}}
}}



Revision as of 13:59, 28 February 2019


Function

Adenosine dimethyltransferase (KsgA) dimethylates two adjacent adenines at the C-terminal of the 16S rRNA in the small 30S ribosomal subunit, thus modifying it. KsgA catalyzes the dimethylation of adenines 1518-1519 using S-adenosyl-methionine (SAM) as the methyl donor and producing S-adenosyl-homocysteine (SAH).

Relevance

KsgA confers resistance to the antibiotic kasugomycin.

Structural highlights

Among methyltransferases, KsgA and the reaction it catalyzes are conserved throughout evolution. However, the specifics of substrate recognition by the enzyme remain unknown. Here we report structures of (SAH, reaction product of cofactor S-adenosylmethionine), revealing critical structural information on KsgA-RNA and KsgA-SAH interactions. Moreover, the structures show how conformational changes that occur upon RNA binding create the cofactor-binding site. There are nine conserved functional motifs (motifs I-VIII and X) in KsgA. Prior to RNA binding, motifs I and VIII are flexible, each exhibiting two distinct conformations. Upon RNA binding, the two motifs become stabilized in one of these conformations, which is compatible with the binding of SAH. Motif X, which is also stabilized upon RNA binding, is directly involved in the binding of SAH.[1]

3D structures of adenosine dimethyltransferase

Adenosine dimethyltransferase 3D structures


Structure of adenosine dimethyltransferase complex with RNA, SAH and K+ ion (purple) (PDB code 3ftf).

Drag the structure with the mouse to rotate

3D structures of adenosine dimethyltransferase3D structures of adenosine dimethyltransferase

Updated on 28-February-2019


ReferencesReferences

  1. Tu C, Tropea JE, Austin BP, Court DL, Waugh DS, Ji X. Structural basis for binding of RNA and cofactor by a KsgA methyltransferase. Structure. 2009 Mar 11;17(3):374-85. PMID:19278652 doi:10.1016/j.str.2009.01.010

Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

Michal Harel, Alexander Berchansky