Format

Send to

Choose Destination
FEBS Lett. 1996 Sep 30;394(2):196-200.

Identification of the histidine residues involved in substrate recognition by a rat H+/peptide cotransporter, PEPT1.

Author information

1
Department of Pharmacy, Kyoto University Hospital, Faculty of Medicine, Japan.

Abstract

The LLC-PK1 cells stably transfected with a rat PEPT1 cDNA transported ceftibuten (anion) and cephradine (zwitterion), both oral beta-lactam antibiotics, in a H+-gradient-dependent manner. Diethylpyrocarbonate, a histidine residue modifier, abolished ceftibuten uptake. This inhibition was prevented in the presence of glycylsarcosine or cephradine. When expressed in Xenopus oocytes, replacement of either histidine 57 or histidine 121 of the rat PEPT1 with glutamine by site-directed mutagenesis eliminated ceftibuten and [14C]glycylsarcosine transport activities. Immunostaining of oocyte sections indicated that insertion of the mutant transporters in the plasma membranes was not impaired. These findings suggest that both histidine 57 and histidine 121, which are conserved in the rat, rabbit and human PEPT1, are involved in substrate recognition of this molecule.

PMID:
8843163
DOI:
10.1016/0014-5793(96)00952-0
[Indexed for MEDLINE]
Free full text

Supplemental Content

Full text links

Icon for Wiley
Loading ...
Support Center