6TZX

Crystal Structure of Fungal RNA Kinase

Summary for 6TZX

• Entry DOI: 10.2210/pdb6tzx/pdb
• Descriptor: tRNA ligase, INOSINE-5'-DIPHOSPHATE, PHOSPHATE ION, ... (4 entities in total)
• Functional Keywords: rna ligase, rna repair, polynucleotide kinase, transferase
• Biological source: Candida albicans (strain SC5314 / ATCC MYA-2876) (Yeast)
• Total number of polymer chains: 1
• Total formula weight: 27700.64

Authors

Shuman, S.,Goldgur, Y.,Banerjee, A. (deposition date: 2019-08-13, release date: 2019-11-06, Last modification date: 2023-10-11)

Primary citation

Banerjee, A.,Goldgur, Y.,Schwer, B.,Shuman, S.
Atomic structures of the RNA end-healing 5'-OH kinase and 2',3'-cyclic phosphodiesterase domains of fungal tRNA ligase: conformational switches in the kinase upon binding of the GTP phosphate donor.
Nucleic Acids Res., 47:11826-11838, 2019

PubMed Abstract: Fungal tRNA ligase (Trl1) rectifies RNA breaks with 2',3'-cyclic-PO4 and 5'-OH termini. Trl1 consists of three catalytic modules: an N-terminal ligase (LIG) domain; a central polynucleotide kinase (KIN) domain; and a C-terminal cyclic phosphodiesterase (CPD) domain. Trl1 enzymes found in all human fungal pathogens are untapped targets for antifungal drug discovery. Here we report a 1.9 Å crystal structure of Trl1 KIN-CPD from the pathogenic fungus Candida albicans, which adopts an extended conformation in which separate KIN and CPD domains are connected by an unstructured linker. CPD belongs to the 2H phosphotransferase superfamily by dint of its conserved central concave β sheet and interactions of its dual HxT motif histidines and threonines with phosphate in the active site. Additional active site motifs conserved among the fungal CPD clade of 2H enzymes are identified. We present structures of the Candida Trl1 KIN domain at 1.5 to 2.0 Å resolution-as apoenzyme and in complexes with GTP•Mg2+, IDP•PO4, and dGDP•PO4-that highlight conformational switches in the G-loop (which recognizes the guanine base) and lid-loop (poised over the nucleotide phosphates) that accompany nucleotide binding.

PubMed: 31722405
DOI: 10.1093/nar/gkz1049

Experimental method

X-RAY DIFFRACTION (1.529 Å)