Interactions between large and small subunits of different acetohydroxyacid synthase isozymes of Escherichia coli

Maria Vyazmensky, Yuri Zherdev, Alex Slutzker, Inna Belenky, Olga Kryukov, Ze'ev Barak, David M. Chipman

Research output: Contribution to journalArticlepeer-review

19 Scopus citations


The large, catalytic subunits (LSUs; ilvB, ilvG and ilvI, respectively) of enterobacterial acetohydroxyacid synthases isozymes (AHAS I, II and III) have molecular weights ∼60 kDa and are paralogous with a family of other thiamin diphosphate dependent enzymes. The small, regulatory subunits (SSUs) of AHAS I and AHAS III (ilvN and ilvH) are required for valine inhibition, but ilvN and ilvH can only confer valine sensitivity on their own LSUs. AHAS II is valine resistant. The LSUs have only ∼15, ≪1 and ∼3%, respectively, of the activity of their respective holoenzymes, but the holoenzymes can be reconstituted with complete recovery of activity. We have examined the activation of each of the LSUs by SSUs from different isozymes and ask to what extent such activation is specific; that is, is effective nonspecific interaction possible between LSUs and SSUs of different isozymes? To our surprise, the AHAS II SSU ilvM is able to activate the LSUs of all three of the isozymes, and the truncated AHAS III SSUs ilvH-Δ80, ilvH-Δ86 and ilvH-Δ89 are able to activate the LSUs of both AHAS I and AHAS III. However, none of the heterologously activated enzymes have any feedback sensitivity. Our results imply the existence of a common region in all three LSUs to which regulatory subunits may bind, as well as a similarity between the surfaces of ilvM and the other SSUs. This surface must be included within the N-terminal βαββαβ-domain of the SSUs, probably on the helical face of this domain. We suggest hypotheses for the mechanism of valine inhibition, and reject one involving induced dissociation of subunits.

Original languageEnglish
Pages (from-to)8731-8737
Number of pages7
Issue number36
StatePublished - 15 Sep 2009

ASJC Scopus subject areas

  • Biochemistry


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