Halide binding site

Tang, L., Torres Pazmino, D.E., Fraaije, M.W., de Jong, R.M., Dijkstra, B.W. and Janssen, D.B., Improved catalytic properties of halohydrin dehalogenase hy modification of the halide-binding site. Biochemistry, 2005, 44, 6609. 

Fiedler TJ, Davey CA, Fenna RE (2000) X-ray crystal structure and characterization of halide-binding sites of human myeloperoxidase at 1.8 A resolution. J Biol Chem 275 11964-11971... 

One particular advantage of in silica mutations is the fact that nonnatural mutations can also be easily introduced, for example, mutations of the backbone to assess the importance of a backbone hydrogen bond donor or acceptor. For example, in the study of the epoxide-opening reaction of the HheC, a backbone amide in the halide-binding site was mutated into an ester to evaluate the importance of the hydrogen bond between the backbone and the nucleophile (see Section 8.20.4.3.4). 

Figure 8.4 adapted from crystallographic coordinates deposited with the Protein Data Bank. PDB ID lEDB. Verschueren, K.H.G., Kingma, J., Rozeboom, H.J., Kalk, K.H., Janssen, D.B., Dijkstra, B.W.D., Crystallographic and Fluorescence Studies of the Interaction of Haloalkane Dehalogenase with Halide Ions Studies with Halide Cmpounds Reveal a Halide Binding Site in the Active Site. 

The mechanism of halohydrin dehalogenase was shown to proceed in a reversible fashion via a push-pull-like nucleophilic attack of halide (provided by a lipophilic halide binding site) with simultaneous activation of the epoxide through protonation by a Tyr residue (Scheme 2.236) [1844, 1845]. 

In a typical experiment where a quadrupolar halide ion is used as a probe in a system of biological interest, site A is usually "free" halide ions in aqueous solution while site B is a halide binding site on a macromolecule. In such an experimental situation the halide nuclei in site A are under conditions of extreme narrowing and consequently... 

In the foregoing section the halide binding sites were tacitly assumed to be present on a protein or some other macromolecule. This assumption is by no means necessary - the halide quadrupole relaxation technique has been applied quite successfully to study halide ion binding also to small molecules of biological importance. 

Anion cryptates are formed by macrotricycles like (5) in their tetraprotonated state with the spherical halide anions [8]. (5)-4H binds the chloride ion very strongly and very selectively, giving the [Cl" c (5)-4H J cryptate (7), but does not complex other types of anions. These properties are unique at present with respect to both synthetic and natural halide binding sites, very little being known about the latter. Non-complementarity between an ellipsoidal cryptand and the spherical halides results in appreciable ligand distortions in the cryptates formed and in lower binding constants [9, 10] (see also below). 

The nature of the halide binding sites in LADH have been in dispute. Ward and Happe (74) assumed that Cl did coordinate directly to the zinc atom at the active site. On the other hand Lindman et al. (73,76,77) concluded that halide coordination to the zinc, if it occurs, has no influence on the halide ion relaxation rate. Their conclusions were based on results from halogen NMR studies in the presence of ligands believed or known to coordinate to the zinc in the active site. Thus neither oxy-quinoline nor ortho-phenanthroline affect the chloride ion relaxation. 

Halide binding site Halide binding site ... 

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