Structural and mechanistic insights into the bifunctional HISN2 enzyme catalyzing the second and third steps of histidine biosynthesis in plants

Witek, Wojciech; Sliwiak, Joanna; Ruszkowski, Milosz

doi:10.1038/s41598-021-88920-2

Structural and mechanistic insights into the bifunctional HISN2 enzyme catalyzing the second and third steps of histidine biosynthesis in plants

Journal Article · Thu May 06 00:00:00 EDT 2021 · Scientific Reports

DOI:https://doi.org/10.1038/s41598-021-88920-2· OSTI ID:1783832

Witek, Wojciech ^[1]; Sliwiak, Joanna ^[1]; Ruszkowski, Milosz ^[2]

Polish Academy of Sciences (PAS), Poznan (Poland)
Polish Academy of Sciences (PAS), Poznan (Poland); National Cancer Institute, Argonne, IL (United States)

The second and third steps of the histidine biosynthetic pathway (HBP) in plants are catalyzed by a bifunctional enzyme–HISN2. The enzyme consists of two distinct domains, active respectively as a phosphoribosyl-AMP cyclohydrolase (PRA-CH) and phosphoribosyl-ATP pyrophosphatase (PRA-PH). The domains are analogous to single-domain enzymes encoded by bacterial hisI and hisE genes, respectively. The calculated sequence similarity networks between HISN2 analogs from prokaryotes and eukaryotes suggest that the plant enzymes are closest relatives of those in the class of Deltaproteobacteria. In this work, we obtained crystal structures of HISN2 enzyme from Medicago truncatula (MtHISN2) and described its architecture and interactions with AMP. The AMP molecule bound to the PRA-PH domain shows positioning of the N1-phosphoribosyl relevant to catalysis. AMP bound to the PRA-CH domain mimics a part of the substrate, giving insights into the reaction mechanism. The latter interaction also arises as a possible second-tier regulatory mechanism of the HBP flux, as indicated by inhibition assays and isothermal titration calorimetry.

View Accepted Manuscript (DOE)

Research Organization:: Argonne National Laboratory (ANL), Argonne, IL (United States). Advanced Photon Source (APS)

Sponsoring Organization:: National Cancer Institute (NCI); National Science Centre; USDOE Office of Science (SC), Biological and Environmental Research (BER)

Grant/Contract Number:: AC02-06CH11357; W-31109-ENG-38

OSTI ID:: 1783832

Alternate ID(s):: OSTI ID: 1818365
OSTI ID: 1785009

Journal Information:: Scientific Reports, Journal Name: Scientific Reports Journal Issue: 1 Vol. 11; ISSN 2045-2322

Publisher:: Nature Publishing GroupCopyright Statement

Country of Publication:: United States

Language:: ENGLISH

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