Characterization of the enzymatic and multifunctional properties of Acinetobacter baumannii erythrose-4-phosphate dehydrogenase (E4PDH)

Ramesh Nimma, Ajay Kumar, Zahid Gani, Anuj Gahlawat, Rahul Dilawari, Rajesh Kumar Rohilla, Hemangi Kumbhar, Prabha Garg, Sidharth Chopra, Manoj Raje, Chaaya Iyengar Raje

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

Abstract

Infections due to Acinetobacter baumannii (A. baumannii) are rapidly increasing worldwide and consequently therapeutic options for treatment are limited. The emergence of multi drug resistant (MDR) strains has rendered available antibiotics ineffective, necessitating the urgent discovery of new drugs and drug targets. The vitamin B6 biosynthetic pathway has been considered as a potential antibacterial drug target but it is as yet uncharacterized for A. baumannii. In the current work, we have carried out in silico and biochemical characterization of Erythrose-4-phosphate dehydrogenase (E4PDH) (EC 1.2.1.72). This enzyme catalyzes the first step in the deoxyxylulose-5-phosphate (DXP) dependent Vitamin B6 biosynthetic pathway i.e. the conversion of D-erythrose-4-phosphate (E4P) to 4-Phosphoerythronate. E4PDH also possesses an additional activity whereby it can catalyze the conversion of Glyceraldehyde-3-phosphate (G3P) to 1,3 bisphosphoglycerate (1,3BPG). Our studies have revealed that this enzyme exhibits an alternate moonlighting function as a cell surface receptor for the human iron transport proteins transferrin (Tf) and lactoferrin (Lf). The present work reports the internalization of Tf and consequent iron acquisition as an alternate strategy for iron acquisition. Given its essential role in two crucial pathways i.e. metabolism and iron acquisition, A. baumannii E4PDH may play a vital role in bacterial pathogenesis.

Original languageEnglish (US)
Article number105992
JournalMicrobial Pathogenesis
Volume175
DOIs
StatePublished - Feb 2023
Externally publishedYes

Keywords

  • Acinetobacter baumannii (A. baumannii)
  • Erythrose-4-phosphate dehydrogenase (E4PDH)
  • Iron
  • Protein multifunctionality
  • Vitamin B6

ASJC Scopus subject areas

  • Microbiology
  • Infectious Diseases

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