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

DIR@IMTECH: CSIR-Institute of Microbial Technology

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Title Characterization of the enzymatic and multifunctional properties of Acinetobacter baumannii erythrose-4-phosphate dehydrogenase (E4PDH)
 
Creator Nimma, Ramesh
Kumar, Ajay
Gani, Zahid
Gahlawat, Anuj
Dilawari, Rahul
Rohilla, Kumar Rajesh
Kumbhar, Hemangi
Garg, Prabha
Chopra, Sidharth
Raje, Manoj
Raje, Chaaya Iyengar
 
Subject QR Microbiology
 
Description 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.
 
Publisher Elsevier Science
 
Date 2023-02
 
Type Article
PeerReviewed
 
Relation https://doi.org/10.1016/j.micpath.2023.105992
http://crdd.osdd.net/open/3098/
 
Identifier Nimma, Ramesh and Kumar, Ajay and Gani, Zahid and Gahlawat, Anuj and Dilawari, Rahul and Rohilla, Kumar Rajesh and Kumbhar, Hemangi and Garg, Prabha and Chopra, Sidharth and Raje, Manoj and Raje, Chaaya Iyengar (2023) Characterization of the enzymatic and multifunctional properties of Acinetobacter baumannii erythrose-4-phosphate dehydrogenase (E4PDH). Microbial pathogenesis, 175. ISSN 0882-4010