7V0F

Structure of 6-carboxy-5,6,7,8-tetrahydropterin synthase paralog QueD2 from Acinetobacter baumannii

Summary for 7V0F

• Entry DOI: 10.2210/pdb7v0f/pdb
• Descriptor: 6-carboxy-5,6,7,8-tetrahydropterin synthase, 1,2-ETHANEDIOL, ZINC ION, ... (5 entities in total)
• Functional Keywords: queuosine, transfer rna, translation elongation, zn metalloenzyme, nutritional immunity, lyase
• Biological source: Acinetobacter baumannii ATCC 17978
• Total number of polymer chains: 2
• Total formula weight: 46643.98

Authors

Jordan, M.R.,Gonzalez-Gutierrez, G.,Giedroc, D.P. (deposition date: 2022-05-10, release date: 2022-12-07, Last modification date: 2024-05-22)

Primary citation

Jordan, M.R.,Gonzalez-Gutierrez, G.,Trinidad, J.C.,Giedroc, D.P.
Metal retention and replacement in QueD2 protect queuosine-tRNA biosynthesis in metal-starved Acinetobacter baumannii.
Proc.Natl.Acad.Sci.USA, 119:e2213630119-e2213630119, 2022

PubMed Abstract: In response to bacterial infection, the vertebrate host employs the metal-sequestering protein calprotectin (CP) to withhold essential transition metals, notably Zn(II), to inhibit bacterial growth. Previous studies of the impact of CP-imposed transition-metal starvation in identified two enzymes in the de novo biosynthesis pathway of queuosine-transfer ribonucleic acid (Q-tRNA) that become cellularly abundant, one of which is QueD2, a 6-carboxy-5,6,7,8-tetrahydropterin (6-CPH) synthase that catalyzes the initial, committed step of the pathway. Here, we show that CP strongly disrupts Q incorporation into tRNA. As such, we compare the QueD2 "low-zinc" paralog with a housekeeping, obligatory Zn(II)-dependent enzyme QueD. The crystallographic structure of Zn(II)-bound QueD2 reveals a distinct catalytic site coordination sphere and assembly state relative to QueD and possesses a dynamic loop, immediately adjacent to the catalytic site that coordinates a second Zn(II) in the structure. One of these loop-coordinating residues is an invariant Cys18, that protects QueD2 from dissociation of the catalytic Zn(II) while maintaining flux through the Q-tRNA biosynthesis pathway in cells. We propose a "metal retention" model where Cys18 introduces coordinative plasticity into the catalytic site which slows metal release, while also enhancing the metal promiscuity such that Fe(II) becomes an active cofactor. These studies reveal a complex, multipronged evolutionary adaptation to cellular Zn(II) limitation in a key Zn(II) metalloenzyme in an important human pathogen.

PubMed: 36442121
DOI: 10.1073/pnas.2213630119

Experimental method

X-RAY DIFFRACTION (2.35 Å)