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Publication Abstract from PubMed

In the first committed step of histidine biosynthesis, ATP and 5-phosphoribosyl-alpha1-pyrophosphate (PRPP), in a presence of ATP phosphoribosyltransferase (ATP-PRT, EC 2.4.2.17), yield phosphoribosyl-ATP. ATP-PRTs are subject to feedback inhibition by histidine, that allosterically binds between the regulatory domains. Histidine biosynthetic pathways of bacteria, lower eukaryotes, and plants are considered promising targets for a design of antibiotics, antifungal agents, and herbicides because higher organisms are histidine heterotrophs. Plant ATP-PRTs are similar to one of the two types of their bacterial counterparts, the long-type ATP-PRTs. A biochemical and structural study of ATP-PRT from the model legume plant, Medicago truncatula ( Medtr ATP-PRT1) is reported herein. Two crystal structures, presenting homohexameric Medtr ATP-PRT1 in its relaxed (R-) and histidine-bound, tense (T-) states allowed to observe key features of the enzyme and provided the first structural insights into an ATP-PRT from a eukaryotic organism. In particular, they show pronounced conformational reorganizations during R-state to T-state transition that involves substantial movements of domains. This rearrangement requires a trans - to cis - switch of a peptide backbone within the hinge region of Medtr ATP-PRT1. A C-terminal alpha-helix, absent in bacteria, reinforces the hinge that is constituted by two peptide strands. As a result, conformations of the R- and T-states are significantly different from the corresponding states of prokaryotic enzymes with known 3-D structures. Lastly, AMP bound at the active site is consistent with a competitive (and synergistic with histidine) nature of AMP inhibition.

Guarding the gateway to histidine biosynthesis in plants: Medicago truncatula ATP-phosphoribosyltransferase in relaxed and tense states.,Ruszkowski M Biochem J. 2018 Aug 2. pii: BCJ20180289. doi: 10.1042/BCJ20180289. PMID:30072492^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.