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Statements

Subject Item
n2:RIV%2F61388963%3A_____%2F14%3A00435073%21RIV15-GA0-61388963
rdf:type
skos:Concept n16:Vysledek
dcterms:description
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 K-M for K+ of about 100 mu M. The presence of potassium ions lowers the apparent K-M of the enzyme for homocysteine, but it does not affect the apparent K-M for betaine or the apparent k(cat) 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. 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 K-M for K+ of about 100 mu M. The presence of potassium ions lowers the apparent K-M of the enzyme for homocysteine, but it does not affect the apparent K-M for betaine or the apparent k(cat) 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.
dcterms:title
Specific potassium ion interactions facilitate homocysteine binding to betaine-homocysteine S-methyltransferase Specific potassium ion interactions facilitate homocysteine binding to betaine-homocysteine S-methyltransferase
skos:prefLabel
Specific potassium ion interactions facilitate homocysteine binding to betaine-homocysteine S-methyltransferase Specific potassium ion interactions facilitate homocysteine binding to betaine-homocysteine S-methyltransferase
skos:notation
RIV/61388963:_____/14:00435073!RIV15-GA0-61388963
n3:aktivita
n14:I n14:P
n3:aktivity
I, P(GAP207/10/1277), P(GBP208/12/G016)
n3:cisloPeriodika
10
n3:dodaniDat
n10:2015
n3:domaciTvurceVysledku
n5:9726411 n5:7286503 n5:2793911 n5:3046486
n3:druhVysledku
n12:J
n3:duvernostUdaju
n15:S
n3:entitaPredkladatele
n6:predkladatel
n3:idSjednocenehoVysledku
46479
n3:idVysledku
RIV/61388963:_____/14:00435073
n3:jazykVysledku
n13:eng
n3:klicovaSlova
BHMT; homocysteine; potassium; crystal structure; molecular dynamics; simulations; enzyme kinetics
n3:klicoveSlovo
n4:molecular%20dynamics n4:BHMT n4:potassium n4:enzyme%20kinetics n4:homocysteine n4:crystal%20structure n4:simulations
n3:kodStatuVydavatele
US - Spojené státy americké
n3:kontrolniKodProRIV
[98A464D345CE]
n3:nazevZdroje
Proteins-Structure, Function and Bioinformatics
n3:obor
n17:CE
n3:pocetDomacichTvurcuVysledku
4
n3:pocetTvurcuVysledku
9
n3:projekt
n11:GAP207%2F10%2F1277 n11:GBP208%2F12%2FG016
n3:rokUplatneniVysledku
n10:2014
n3:svazekPeriodika
82
n3:tvurceVysledku
Mládková, Jana Hladílková, Jana Jiráček, Jiří Yamada, K. Tryon, K. Jungwirth, Pavel Koutmos, M. Diamond, C. E. Garrow, T. A.
n3:wos
000342849400022
s:issn
0887-3585
s:numberOfPages
13
n18:doi
10.1002/prot.24619