Promise: a new database of information on prosthetic centres and metal ions in protein active sites.

The PROMISE (Prosthetic centres and metal ions in protein active sites) database aims to gather together comprehensive sequence, structural, functional and bibliographic information on proteins which possess prosthetic centres, with an emphasis on active site structure and function. The database is available on the World Wide Web at http://bioinf.leeds. ac.uk/promise/ BACKGROUND Of the more than 5000 proteins of known three-dimensional structure, at least half contain metal ions or other non-protein prosthetic groups in their active sites; such prosthetic groups often themselves containing metal ions. Nature has made abundant use of the wide range of chemical properties of the elements, exemplified conspicuously by the complex coordination states of the transition metals. The presence of metal ions and other prosthetic groups confers vitally important properties on the proteins concerned, while the protein environments of the groups modulate the chemistry of the ions in subtle ways. The ‘tuning’ of the chemical reactivity of catalytic centres to the needs of the organism by this interplay of the protein and non-protein components is clearly highly sensitive to the local geometry of the active sites and further modified by the overall molecular structure. The genome sequencing and other structural biology projects are accumulating ever more data, but the need to systematise and analyse the data becomes correspondingly more demanding. In addition to the rapidly growing ‘primary’ databanks of nucleic acid and protein sequences (corresponding already to >150 000 different proteins) and the Protein Databank of three-dimensional (3-D) structures, a number of ‘secondary’ databases have been derived, covering a diverse array of specialised areas. These include classification of proteins in terms of invariant active site groups (3), of ‘fingerprints’ of complex sequence motifs ( 1) or of patterns of chain fold ( 13,19). The PROMISE database is uniquely focused on protein active site structure and on the relationships between protein molecules and non-protein prosthetic centres, combining the relevant sequence, 3-D structural and physico-chemical information (7). The concept of bioinorganic motif (14), a structural feature peculiar for metalloproteins and other complex proteins, may be useful in further discussion. Bioinorganic motifs, some of which are exemplified in Figure 1, endow a protein with function(s) possessed by neither the apoprotein nor prosthetic group alone. These motifs are quite different from sequence motifs (basically strings of text) or protein fold motifs (such as βαβ or HTH motifs). Although there are many families of proteins sharing both fold and bioinorganic motif, there are also evolutionarily unrelated but functionally analogous systems which have similar bioinorganic motif and, vice versa, there are proteins which share the same fold but have distinct active site structures. Bioinorganic motifs often possess unique spectroscopic properties which make it possible to study them relatively independently from the rest of the protein matrix.