Coordination environment changes of the vanadium in vanadium-dependent haloperoxidase enzymes

• Published in: Journal of inorganic biochemistry 2018-09, Vol.186, p.267-279
• Main Authors: McLauchlan, Craig C., Murakami, Heide A., Wallace, Craig A., Crans, Debbie C.
• Format: Article
• Language: English
• Subjects: Animals; Catalysis; Catalytic Domain; Chloride Peroxidase - chemistry; Chloride Peroxidase - metabolism; Coordination chemistry; Five-coordinate; Halogens - chemistry; Halogens - metabolism; Haloperoxidase; Humans; Mechanism; Oxidation-Reduction; Peroxidases - chemistry; Peroxidases - metabolism; Peroxidovanadium; Vanadium; Vanadium - chemistry; Vanadium - metabolism
• ISSN: 0162-0134; 1873-3344
• DOI: 10.1016/j.jinorgbio.2018.06.011

Vanadium-dependent haloperoxidases are a class of enzymes that catalyze oxidation reactions with halides to form halogenated organic products and water. These enzymes include chloroperoxidase and bromoperoxidase, which have very different protein sequences and sizes, but regardless the coordination environment of the active sites is surprisingly constant. In this manuscript, the comparison of the coordination chemistry of V-containing-haloperoxidases of the trigonal bipyramidal geometry was done by data mining. The catalytic cycle imposes changes in the coordination geometry of the vanadium to accommodate the peroxidovanadium(V) intermediate in an environment we describe as a distorted square pyramidal geometry. During the catalytic cycle, this intermediate converts to a trigonal bipyramidal intermediate before losing the halogen and forming a tetrahedral vanadium-protein intermediate. Importantly, the catalysis is facilitated by a proton-relay system supplied by the second sphere coordination environment and the changes in the coordination environment of the vanadium(V) making this process unique among protein catalyzed processes. The analysis of the coordination chemistry shows that the active site is very tightly regulated with only minor changes in the coordination geometry. The coordination geometry in the protein structures deviates from that found for both small molecules crystalized in the absence of protein and the reported functional small molecule model compounds. At this time there are no examples reported of a structurally similar small molecule with the geometry observed for the peroxidovanadium(V) in the active site of the vanadium-containing haloperoxidases. The coordination chemistry of the vanadium-haloperoxidase protein complexes is important for the catalysis. Datamining was used to characterize the detail of the changes in the coordination chemistry with the different protein‑vanadium complexes, and compared to x-ray structures of small molecules to document the role of the protein. [Display omitted] •Datamining was carried out of vanadium-bound haloperoxidases.•Vanadium-protein complexes had the vanadium in a trigonal bipyramidal-5 geometry.•Vanadium-protein complexes had the peroxidovanadium in a square pyramidal-5 geometry.•No molecule exists with the geometry found in vanadium-haloperoxidase active sites.•Coordination chemistry is important for the mechanism of the enzyme catalyzed reaction.