Crystal Structure of Cobalt-Containing Nitrile Hydratase

The Redox Biochemistry of Protein Sulfenylation and Sulfinylation

“…Structural analysis reveals that NHase contains an Fe III or Co III active site, in which three Cys residues, with three different oxidation states (RSH, RSOH, and RSO 2 H), contribute to the coordination of the metal ion (74,75). The fully reduced enzyme appears inactive, suggesting that Cys sulfenylation and sulfinylation are critical in maintaining the catalytic activity of NHase (76), probably by increasing the Lewis acidity of the metal ion.…”

Analyzing the catalytic role of active site residues in the Fe-type nitrile hydratase from Comamonas testosteroni Ni1

“…1,6,7 The metal ion is ligated by three cysteine sulfur atoms, two backbone amide nitrogens, and a water molecule. [8][9][10][11] Two of the active site cysteine residues are post-translationally modified to cysteine-sulfinic acid (Cys-SO2H) and cysteine-sulfenic acid (Cys-SOH) yielding an unusual metal coordination geometry, termed the "claw-setting". 8,9 Recently, X-ray crystal structures of a Co-type NHase from Pseudonocardia thermophila JCM 3095(PtNHase) bound by butane boronic acid and phenylboronic acid revealed a covalent bond between the oxygen atom of the sulfenic acid ligand and the boron atom of the boronic acid.…”

“…[8][9][10][11] Two of the active site cysteine residues are post-translationally modified to cysteine-sulfinic acid (Cys-SO2H) and cysteine-sulfenic acid (Cys-SOH) yielding an unusual metal coordination geometry, termed the "claw-setting". 8,9 Recently, X-ray crystal structures of a Co-type NHase from Pseudonocardia thermophila JCM 3095(PtNHase) bound by butane boronic acid and phenylboronic acid revealed a covalent bond between the oxygen atom of the sulfenic acid ligand and the boron atom of the boronic acid. 12 These data provided the first experimental evidence that the sulfenic acid ligand can function as a nucleophile, which was supported by DFT calculations 13 and QM/MM studies.…”

Incorporation of thiolate donation using 2,2′-dithiodibenzaldehyde: Complexes of a pentadentate N2S3 ligand with relevance to the active site of Co nitrile hydratase

“…Examples include nitrile hydratase [1][2][3][4][5][6][7][8][9][10] and the A-cluster of carbon monoxide dehydrogenase/acetyl CoA synthase [11][12][13][14][15][16][17][18][19][20][21][22][23]. Understanding the catalytic mechanisms of these enzymes can be greatly aided by the study of small-molecule analogs, or model complexes, which reproduce the active-site structure and/or the function of the enzyme.…”

“…The nitrile hydratase enzymes, which catalyze the hydrolysis of nitriles to amides, have an active site consisting of either Co(III) or Fe(III) in an N 2 S 3 X coordination sphere comprised of two deprotonated amide N donors from the protein backbone, three cysteine thiolates, two of which have been post-translationally modified to sulfenic and sulfinic acid groups, and an exogenous hydroxide ligand [10,[27][28]. This unusual active site geometry is likely to be relevant in terms of tuning the electronics of the active-site metal.…”