7v0f | pdb_00007v0f

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

spinqualitylabelsall models 7v0f, resolution 2.35Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 7v0f is a 2 chain structure with sequence from Acinetobacter baumannii ATCC 17978. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: EDO, PEG, ZN Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function A0A081GYS3_ACIBA Publication Abstract from PubMed 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 A. baumannii 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(4)) 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 AbQueD2 "low-zinc" paralog with a housekeeping, obligatory Zn(II)-dependent enzyme QueD. The crystallographic structure of Zn(II)-bound AbQueD2 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. Metal retention and replacement in QueD2 protect queuosine-tRNA biosynthesis in metal-starved Acinetobacter baumannii.,Jordan MR, Gonzalez-Gutierrez G, Trinidad JC, Giedroc DP Proc Natl Acad Sci U S A. 2022 Dec 6;119(49):e2213630119. doi: , 10.1073/pnas.2213630119. Epub 2022 Nov 29. PMID:36442121 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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