31lq | pdb_000031lq
Crystal structure of Geobacillus thermodenitrificans YqeK in complex with ADP
Structural highlights
FunctionPublication Abstract from PubMedDiadenosine tetraphosphate (Ap(4)A) and related dinucleoside tetraphosphates (Ap(4)Ns) are important stress-signaling molecules that coordinate bacterial adaptation to changing environmental conditions. Although the enzymes for turnover of Ap(4)A are known in several bacteria, the structural basis for substrate recognition and the cellular consequences of impaired Ap(4)A turnover remain poorly understood. Here, we characterize the Histidine-Aspartate (HD)-domain hydrolase YqeK from Bacillus subtilis. Deletion of yqeK impaired growth in stationary phase, sporulation, and biofilm formation, demonstrating a general role under nutrient limitation. YqeK forms a homodimer and functions as a manganese-dependent phosphohydrolase, symmetrically cleaving Ap(4)A into two ADP molecules and removing Ap(4)A caps from RNA. The enzyme was active not only toward Ap(4)A but also toward the mixed dinucleotides Ap(4)G, Ap(4)C, and Ap(4)U in both in vitro and in vivo assays, hence acting as a broad-spectrum regulator of Ap(4)N homeostasis. To understand this promiscuity, we determined crystal structures of YqeK in its apo- and ADP-bound state and in complex with a non-hydrolysable Ap(4)A analogue. The structures revealed an asymmetric recognition mechanism in which one nucleoside moiety and the proximal phosphate groups are tightly coordinated, whereas the distal nucleoside is accommodated largely through nonspecific interactions, explaining the ability of YqeK to process diverse substrates. Together, our findings establish YqeK as a central regulator of dinucleotide homeostasis and RNA metabolism and provide the structural framework for Ap(4)N recognition by HD-domain phosphohydrolases. Molecular insights into the promiscuous Ap(4)N hydrolase YqeK.,Shivakumar RD, Happel N, Burchert F, Bruck M, Randau L, Pane-Farre J, Linne U, Freitag J, Hinrichs R, Kiontke S, Bange G, Bedrunka-Meinert P J Biol Chem. 2026 Aug 25;302(10):113490. doi: 10.1016/j.jbc.2026.113490. PMID:42641892[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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