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2016 Pey CBS WT D516-525 AdoMet binding oligomerization.pdf (727.11 kB)

Oligomeric status of human cystathionine beta-synthase modulates AdoMet binding

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journal contribution
posted on 2019-03-05, 01:30 authored by Angel L. Pey, Luis Alfonso Martínez-Cruz, Jan P. Kraus, Tomas Majtan
Cystathionine beta-synthase (CBS) plays a key role in the metabolism of sulfur-containing amino acids. CBS is a multidomain tetrameric enzyme allosterically activated by S-adenosylmethionine (AdoMet). Recent crystallographic analyses of engineered CBS lacking the loop made up of residues 516–525 revealed discrepancies in AdoMet binding compared to previous biophysical studies on a full-length CBS. Here, we show that removal of the loop 516–525 functionally eliminates the high affinity sites responsible for kinetic stabilization of the full-length enzyme and yields a dimeric AdoMet-inducible enzyme, in which kinetic stabilization is now exerted by AdoMet binding to the remaining low affinity sites.


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