The sodium/proline transporter PutP of Helicobacter pylori. Academic Article uri icon

Overview

abstract

  • Helicobacter pylori is cause of chronic gastritis, duodenal ulcer and gastric carcinoma in humans. L-proline is a preferred energy source of the microaerophilic bacterium. Previous analyses revealed that HpputP and HpputA, the genes that are predicted to play a central role in proline metabolism as they encode for the proline transporter and proline dehydrogenase, respectively, are essential for stomach colonization. Here, the molecular basis of proline transport in H. pylori by HpPutP was investigated experimentally for the first time. Measuring radiolabeled substrate transport in H. pylori and E. coli heterologously expressing HpputP as well as in proteoliposomes reconstituted with HpPutP, we demonstrate that the observed proline transport in H. pylori is mediated by HpPutP. HpPutP is specific and exhibits a high affinity for L-proline. Notably, L-proline transport is exclusively dependent on Na(+) as coupling ion, i.e., Na(+)/L-proline symport, reminiscent to the properties of PutP of E. coli even though H. pylori lives in a more acidic environment. Homology model-based structural comparisons and substitution analyses identified amino acids crucial for function. HpPutP-catalyzed proline uptake was efficiently inhibited by the known proline analogs 3,4-dehydro-D,L-proline and L-azetidine-2-carboxylic acid.

publication date

  • December 17, 2013

Research

keywords

  • Amino Acid Transport Systems, Neutral
  • Helicobacter pylori
  • Proline
  • Sodium
  • Symporters

Identity

PubMed Central ID

  • PMC3866251

Scopus Document Identifier

  • 84892916355

Digital Object Identifier (DOI)

  • 10.1038/nature10737

PubMed ID

  • 24358297

Additional Document Info

volume

  • 8

issue

  • 12