Structure-function analysis of the histidine permease and comparison with cystic fibrosis mutations - PubMed (original) (raw)

Comparative Study

. 1991 Oct 5;266(28):18714-9.

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Comparative Study

Structure-function analysis of the histidine permease and comparison with cystic fibrosis mutations

V Shyamala et al. J Biol Chem. 1991.

Free article

Abstract

Traffic ATPases constitute a superfamily of transporters that include prokaryotic permeases and medically important eukaryotic proteins, such as the multidrug resistance P-glycoprotein and the cystic fibrosis gene product. We present a structure-function analysis of a member of this superfamily, the prokaryotic histidine permease, using mutations generated both in vitro and in vivo, and assaying several biochemical functions. The analysis supports a previously predicted structural model and allows the assignment of specific functions to several predicted structural features. Mutations in the secondary structure features which form the nucleotide-binding pocket in general cause the loss of ATP binding activity. Mutations in the helical domain retain ATP binding activity. Several mutations have been identified which may affect the signaling mechanism between ATP hydrolysis and membrane translocation. We relate our findings to those emerging from the recent biochemical and genetic analyses of cystic fibrosis mutations.

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