4m3p

<div style="background-color:#fffaf0;">

== Publication Abstract from PubMed ==

Betaine-homocysteine S-methyltransferase (BHMT) is a zinc-dependent methyltransferase that uses betaine as the methyl donor for the remethylation of homocysteine to form methionine. This reaction supports S-adenosylmethionine biosynthesis, which is required for hundreds of methylation reactions in humans. Herein we report that BHMT is activated by potassium ions with an apparent KM for K+ of about 100 microM. The presence of potassium ions lowers the apparent KM of the enzyme for homocysteine, but it does not affect the apparent KM for betaine or the apparent kcat for either substrate. We employed molecular dynamics (MD) simulations to theoretically predict and protein crystallography to experimentally localize the binding site(s) for potassium ion(s). Simulations predicted that K+ ion would interact with residues Asp26 and/or Glu159. Our crystal structure of BHMT bound to homocysteine confirms these sites of interaction and reveals further contacts between K+ ion and BHMT residues Gly27, Gln72, Gln247, and Gly298. The potassium binding residues in BHMT partially overlap with the previously identified DGG (Asp26-Gly27-Gly28) fingerprint in the Pfam 02574 group of methyltransferases. Subsequent biochemical characterization of several site-specific BHMT mutants confirmed the results obtained by the MD simulations and crystallographic data. Together, the data herein indicate that the role of potassium ions in BHMT is structural and that potassium ion facilitates the specific binding of homocysteine to the active site of the enzyme. Proteins 2014. (c) 2014 Wiley Periodicals, Inc.

Specific potassium ion interactions facilitate homocysteine binding to betaine-homocysteine S-methyltransferase.,Mladkova J, Hladilkova J, Diamond CE, Tryon K, Yamada K, Garrow TA, Jungwirth P, Koutmos M, Jiracek J Proteins. 2014 Jun 4. doi: 10.1002/prot.24619. PMID:24895213<ref>PMID:24895213</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>

</div>

<div class="pdbe-citations 4m3p" style="background-color:#fffaf0;"></div>

== References ==

<references/>