Article ; Online: Characterization of the enzymatic and multifunctional properties of Acinetobacter baumannii erythrose-4-phosphate dehydrogenase (E4PDH).
2023 Volume 175, Page(s) 105992
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, ... ...
| 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. |
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| MeSH term(s) | Humans ; Acinetobacter baumannii ; Anti-Bacterial Agents/pharmacology ; Iron/metabolism ; Vitamin B 6 ; Oxidoreductases ; Phosphates/pharmacology ; Drug Resistance, Multiple, Bacterial | |||||
| Chemical Substances | erythrose (X3EI0WE8Q4) ; Anti-Bacterial Agents ; Iron (E1UOL152H7) ; Vitamin B 6 (8059-24-3) ; Oxidoreductases (EC 1.-) ; Phosphates | |||||
| Language | English | |||||
| Publishing date | 2023-01-14 | |||||
| Publishing country | England | |||||
| Document type | Journal Article | |||||
| ZDB-ID | 632772-2 | |||||
| ISSN | 1096-1208 ; 0882-4010 | |||||
| ISSN (online) | 1096-1208 | |||||
| ISSN | 0882-4010 | |||||
| DOI | 10.1016/j.micpath.2023.105992 | |||||
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| Database | MEDical Literature Analysis and Retrieval System OnLINE |
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