Hexakis(1-benzyl-1H-imidazole-κN3)manganese(II) bis(perchlorate)

Dong, Gui‐Ying; Liu, Tong-Fei; He, C.; Deng, Xiaojuan; Shi, Xiao-Ge

doi:10.1107/s1600536811023531

Cited by 2 publications

(2 citation statements)

References 6 publications

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“…The electron density and anomalous density maps (Figure C–E) indicate that Mn(II) is coordinated only by the high-affinity His 6 site comprising His17 and His27 from S100A8 and His91, His95, His103, and His105 from S100A9. The structural attributes of this octahedral Mn(II)-binding site are in excellent agreement with structurally characterized small-molecule Mn(II) hexaimidazole complexes − as well as a recently reported structure of Mn(II)-bound CP-Ser (PDB 4GGF) (Tables S4 and S5). In contrast to the 4GGF structure, which revealed Mn(II) bound to the His 3 Asp site with 50% occupancy in three of the four heterodimers of the asymmetric unit, our crystallization conditions result in no electron density corresponding to a bound metal ion at the low-affinity Mn(II) site (Figure C).…”

Section: Resultssupporting

confidence: 86%

Manganese Binding Properties of Human Calprotectin under Conditions of High and Low Calcium: X-ray Crystallographic and Advanced Electron Paramagnetic Resonance Spectroscopic Analysis

Gagnon

Brophy²,

Bowman³

et al. 2015

J. Am. Chem. Soc.

183

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The antimicrobial protein calprotectin (CP), a hetero-oligomer of the S100 family members S100A8 and S100A9, is the only identified mammalian Mn(II)-sequestering protein. Human CP uses Ca(II) ions to tune its Mn(II) affinity at a biologically unprecedented hexahistidine site that forms at the S100A8/S100A9 interface, and the molecular basis for this phenomenon requires elucidation. Herein, we investigate the remarkable Mn(II) coordination chemistry of human CP using X-ray crystallography as well as continuous wave (CW) and pulse electron paramagnetic resonance (EPR) spectroscopies. An X-ray crystallographic structure of Mn(II)-CP containing one Mn(II), two Ca(II), and two Na(I) ions per CP heterodimer is reported. The CW EPR spectrum of Ca(II)- and Mn(II)-bound CP prepared with a 10:0.9:1 Ca(II):Mn(II):CP ratio is characterized by an unusually low zero-field splitting of 485 MHz (E/D = 0.30) for the S = 5/2 Mn(II) ion, consistent with the high symmetry of the His6 binding site observed crystallographically. Results from electron spin-echo envelope modulation and electron nuclear double resonance experiments reveal that the six Mn(II)-coordinating histidine residues of Ca(II)- and Mn(II)-bound CP are spectroscopically equivalent. The observed 15N (I = 1/2) hyperfine couplings (A) arise from two distinct classes of nitrogen atoms: the coordinating ε-nitrogen of the imidazole ring of each histidine ligand (A = [3.45, 3.71, 5.91] MHz) and the distal δ-nitrogen (A = [0.11, 0.18, 0.42] MHz). In the absence of Ca(II), the binding affinity of CP for Mn(II) drops by ca. two orders of magnitude and coincides with Mn(II) binding at the His6 site as well as other sites. This study demonstrates the role of Ca(II) in enabling high-affinity and specific binding of Mn(II) to the His6 site of human calprotectin.

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Section: Resultssupporting

confidence: 86%

Manganese Binding Properties of Human Calprotectin under Conditions of High and Low Calcium: X-ray Crystallographic and Advanced Electron Paramagnetic Resonance Spectroscopic Analysis

Gagnon

Brophy²,

Bowman³

et al. 2015

J. Am. Chem. Soc.

183

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“…Of these structures, we identified six compounds with hexaimidazole motifs. 86–91 These complexes exhibit Mn(II) ligated by either unsubstituted or N- substituted imidazoles, and the Mn—N bond lengths span the 2.16 to 2.37 Å range. For example, hexakis(imidazole) manganese(II) dichloride tetrahydrate, {[Mn(C 3 H 4 N 2 ) 6 ]Cl 2 •4H 2 O},86 exhibits Mn—N bond lengths of ca.…”

Section: Summary and Perspectivesmentioning

confidence: 99%

Contributions of the S100A9 C-Terminal Tail to High-Affinity Mn(II) Chelation by the Host-Defense Protein Human Calprotectin

et al. 2013

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Human calprotectin (CP) is an antimicrobial protein that coordinates Mn(II) with high affinity in a Ca(II)-dependent manner at an unusual histidine-rich site (site 2) formed at the S100A8/S100A9 dimer interface. We present a 16-member CP mutant family where mutations in the S100A9 C-terminal tail (residues 96–114) are employed to evaluate the contributions of this region, which houses three histidines and four acidic residues, to Mn(II) coordination at site 2. The results from analytical size-exclusion chromatography, Mn(II) competition titrations, and electron paramagnetic resonance spectroscopy establish that the C-terminal tail is essential for high-affinity Mn(II) coordination by native CP in solution. The studies indicate that His103 and His105 (HXH motif) of the tail complete the Mn(II) coordination sphere in solution, affording an unprecedented biological His6 site. These solution studies are in agreement with a Mn(II)-CP crystal structure reported recently (PNAS 2013, 110, 3841). Remarkably high-affinity Mn(II) binding is retained when either H103 or H105 are mutated to Ala, when the HXH motif is shifted from positions 103–105 to 104–106, and when the human tail is substituted by the C-terminal tail of murine S100A9. Nevertheless, antibacterial activity assays employing human CP mutants reveal that the native disposition of His residues is important for conferring growth inhibition against Escherichia coli and Staphylococcus aureus. Within the S100 family, the S100A8/S100A9 heterooligomer is essential for providing high-affinity Mn(II) binding; the S100A7ox, S100A9(C3S), S100A12, and S100B homodimers do not exhibit such Mn(II)-binding capacity.

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Hexakis(1-benzyl-1H-imidazole-κN³)manganese(II) bis(perchlorate)

Cited by 2 publications

References 6 publications

Manganese Binding Properties of Human Calprotectin under Conditions of High and Low Calcium: X-ray Crystallographic and Advanced Electron Paramagnetic Resonance Spectroscopic Analysis

Manganese Binding Properties of Human Calprotectin under Conditions of High and Low Calcium: X-ray Crystallographic and Advanced Electron Paramagnetic Resonance Spectroscopic Analysis

Contributions of the S100A9 C-Terminal Tail to High-Affinity Mn(II) Chelation by the Host-Defense Protein Human Calprotectin

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