Title : X-ray crystal structure and characterization of halide-binding
sites of human
myeloperoxidase at 1.8 A resolution
Abstract :
- The x-ray crystal structure of human myeloperoxidase has been extended to 1.8 A resolution, using x-ray data recorded at -180 degrees C (r = 0.197, free r = 0.239)
- Results confirm that the heme is covalently attached to the protein via two ester linkages between the carboxyl groups of Glu(242) and Asp(94) and modified methyl groups on pyrrole rings A and C of the heme as well as a sulfonium ion linkage between the sulfur atom of Met(243) and the beta-carbon of the vinyl group on pyrrole ring A
- In the native enzyme a bound chloride ion has been identified at the amino terminus of the helix containing the proximal His(336)
- Determination of the x-ray crystal structure of a myeloperoxidase-bromide complex (r = 0.243, free r = 0.296) has shown that this chloride ion can be replaced by bromide
- Bromide is also seen to bind, at partial occupancy, in the distal heme cavity, in close proximity to the distal His(95) , where it replaces the water molecule hydrogen bonded to Gln(91)
- The bromide-binding site in the distal cavity appears to be the halide-binding site responsible for shifts in the Soret band of the absorption spectrum of myeloperoxidase
- It is proposed that halide binding to this site inhibits the enzyme by effectively competing with H(2) O(2) for access to the distal histidine , whereas in compound I, the same site may be the halide substrate-binding site
Output (sent_index, trigger,
protein,
sugar,
site):
Output(Part-Of) (sent_index,
protein,
site):
- 0. myeloperoxidase, sites
*Output_Site_Fusion* (sent_index,
protein,
sugar,
site):