The x-ray crystal structure of human myeloperoxidase has been extended to 1.8 Å resolution, using x-ray data recorded at ؊180°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 ␤-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 halidebinding 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.

The 1.9 A X-ray crystal structure of human myeloperoxidase complexed with cyanide (R = 0.175, R(free) = 0.215) indicates that cyanide binds to the heme iron with a bent Fe-C-N angle of approximately 157 degrees, and binding is accompanied by movement of the iron atom by 0.2 A into the porphyrin plane. The bent orientation of the cyanide allows the formation of three hydrogen bonds between its nitrogen atom and the distal histidine as well as two water molecules in the distal cavity. The 1.85 A X-ray crystal structure of an inhibitory complex with thiocyanate (R = 0.178, R(free) = 0.210) indicates replacement of chloride at a proximal helix halide binding site in addition to binding in the distal cavity in an orientation parallel with the heme. The thiocyanate replaces two water molecules in the distal cavity and is hydrogen bonded to Gln 91. The 1.9 A structures of the complexes formed by bromide (R = 0.215, R(free) = 0.270) and thiocyanate (R = 0.198, R(free) = 0.224) with the cyanide complex of myeloperoxidase show how the presence of bound cyanide alters the binding site for bromide in the distal heme cavity, while having little effect on thiocyanate binding. These results support a model for a single common binding site for halides and thiocyanate as substrates or as inhibitors near the delta-meso carbon of the porphyrin ring in myeloperoxidase.

WormBook () is an open-access, online collection of original, peer-reviewed chapters on the biology of Caenorhabditis elegans and related nematodes. Since WormBook was launched in June 2005 with 12 chapters, it has grown to over 100 chapters, covering nearly every aspect of C.elegans research, from Cell Biology and Neurobiology to Evolution and Ecology. WormBook also serves as the text companion to WormBase, the C.elegans model organism database. Objects such as genes, proteins and cells are linked to the relevant pages in WormBase, providing easily accessible background information. Additionally, WormBook chapters contain links to other relevant topics in WormBook, and the in-text citations are linked to their abstracts in PubMed and full-text references, if available. Since WormBook is online, its chapters are able to contain movies and complex images that would not be possible in a print version. WormBook is designed to keep up with the rapid pace of discovery in the field of C.elegans research and continues to grow. WormBook represents a generic publishing infrastructure that is easily adaptable to other research communities to facilitate the dissemination of knowledge in the field.

WormBase (www.wormbase.org) is the major publicly available database of information about Caenorhabditis elegans, an important system for basic biological and biomedical research. Derived from the initial ACeDB database of C. elegans genetic and sequence information, WormBase now includes the genomic, anatomical and functional information about C. elegans, other Caenorhabditis species and other nematodes. As such, it is a crucial resource not only for C. elegans biologists but the larger biomedical and bioinformatics communities. Coverage of core areas of C. elegans biology will allow the biomedical community to make full use of the results of intensive molecular genetic analysis and functional genomic studies of this organism. Improved search and display tools, wider cross-species comparisons and extended ontologies are some of the features that will help scientists extend their research and take advantage of other nematode species genome sequences.