Preparation of the Oxidized and Reduced Forms of Psoriasin (S100A7).

Human S100A7 (psoriasin) is a metal-chelating host-defense protein expressed by epithelial cells. S100A7 possesses two Cys residues that generate two redox isoforms of the protein. In the oxidized form (S100A7), Cys47 and Cys96 form an intramolecular disulfide bond, whereas these residues exist as free thiols in the reduced form (S100A7).

Bioinorganic Explorations of Zn(II) Sequestration by Human S100 Host-Defense Proteins.

The human innate immune system launches a metal-withholding response to starve invading microbial pathogens of essential metal nutrients. Zn(II)-sequestering proteins of the human S100 family contribute to this process and include calprotectin (CP, S100A8/S100A9 oligomer, calgranulin A/B oligomer), S100A12 (calgranulin C), and S100A7 (psoriasin). This Perspective highlights recent advances in the Zn(II) coordination chemistry of these three proteins, as well as select studies that evaluate Zn(II) sequestration as an antimicrobial mechanism.

A Method for Selective Depletion of Zn(II) Ions from Complex Biological Media and Evaluation of Cellular Consequences of Zn(II) Deficiency.

We describe the preparation, evaluation, and application of an S100A12 protein-conjugated solid support, hereafter the "A12-resin", that can remove 99% of Zn(II) from complex biological solutions without significantly perturbing the concentrations of other metal ions. The A12-resin can be applied to selectively deplete Zn(II) from diverse tissue culture media and from other biological fluids, including human serum. To further demonstrate the utility of this approach, we investigated metabolic, transcriptomic, and metallomic responses of HEK293 cells cultured in medium depleted of Zn(II) using S100A12.

Biochemical and Functional Evaluation of the Intramolecular Disulfide Bonds in the Zinc-Chelating Antimicrobial Protein Human S100A7 (Psoriasin).

Human S100A7 (psoriasin) is a metal-chelating protein expressed by epithelial cells. It is a 22-kDa homodimer with two EF-hand domains per subunit and two transition-metal-binding HisAsp sites at the dimer interface. Each subunit contains two cysteine residues that can exist as free thiols (S100A7) or as an intramolecular disulfide bond (S100A7).

The Hexahistidine Motif of Host-Defense Protein Human Calprotectin Contributes to Zinc Withholding and Its Functional Versatility.

Human calprotectin (CP, S100A8/S100A9 oligomer, MRP-8/MRP-14 oligomer) is an abundant host-defense protein that is involved in the metal-withholding innate immune response. CP coordinates a variety of divalent first-row transition metal ions, which is implicated in its antimicrobial function, and its ability to sequester nutrient Zn(II) ions from microbial pathogens has been recognized for over two decades. CP has two distinct transition-metal-binding sites formed at the S100A8/S100A9 dimer interface, including a histidine-rich site composed of S100A8 residues His17 and His27 and S100A9 residues His91 and His95.

Calcium Ions Tune the Zinc-Sequestering Properties and Antimicrobial Activity of Human S100A12.

Human S100A12 is a host-defense protein expressed and released by neutrophils that contributes to innate immunity. Apo S100A12 is a 21-kDa antiparallel homodimer that harbors two Ca(II)-binding EF-hand domains per subunit and exhibits two HisAsp motifs for chelating transition metal ions at the homodimer interface. In this work, we present results from metal-binding studies and microbiology assays designed to ascertain whether Ca(II) ions modulate the Zn(II)-binding properties of S100A12 and further evaluate the antimicrobial properties of this protein.

High-affinity manganese coordination by human calprotectin is calcium-dependent and requires the histidine-rich site formed at the dimer interface.

Calprotectin (CP) is a transition metal-chelating antimicrobial protein of the calcium-binding S100 family that is produced and released by neutrophils. It inhibits the growth of various pathogenic microorganisms by sequestering the transition metal ions manganese and zinc. In this work, we investigate the manganese-binding properties of CP.

Fe(CO)4 and related compounds as isolobal fragments.

The M(CO)(4) fragment can be assigned to be isolobal with both CH(3)(+) and CH(2). In order to investigate this ambiguous isolobal assignment, we report calculations on compounds of the type M(CO)(4)L(n), where M is Fe (n = 0), Mn (n = -1), and Co (n = +1) and L is an η(2) ligand with a π bond, generally an alkene. The L's are varied in electron-withdrawing ability, and patterns in computed structural parameters are investigated.