6tzx

From Proteopedia

Crystal Structure of Fungal RNA Kinase

Structural highlights

6tzx is a 1 chain structure with sequence from Candida albicans SC5314. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 1.529Å
Ligands:	,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

TRNL_CANAL One of the two proteins required for the splicing of precursor tRNA molecules containing introns. The ligation activity requires three enzymatic activities: phosphorylation of the 5' terminus of the 3' half-tRNA in the presence of ATP, opening of the 2'3'-cyclic phosphodiester bond of the 5' half-tRNA leaving a 2'-phosphomonoester and ligation of the two tRNA halves in an ATP-dependent reaction.

Publication Abstract from PubMed

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 A 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 beta 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 A 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.

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.,Banerjee A, Goldgur Y, Schwer B, Shuman S Nucleic Acids Res. 2019 Nov 13. pii: 5624966. doi: 10.1093/nar/gkz1049. PMID:31722405^[1]

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

References

↑ 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. 2019 Nov 13. pii: 5624966. doi: 10.1093/nar/gkz1049. PMID:31722405 doi:http://dx.doi.org/10.1093/nar/gkz1049