What is the structure and mechanism of interaction of the zinc finger metal bridge domains with nucleic acids? This question is addressed through a detailed structural analysis of the finger regions from several known nucleic acid binding proteins. A database of zinc finger proteins has been assembled for the purpose of statistical and structural modeling of the individual finger regions. The Zinc Finger Database was established to accumulate a complete collection of potential zinc finger gene sequences that could be rapidly searched by the members of the research community to prevent a major duplication of sequencing efforts. This collection contains both published and unpublished gene sequence data. The database is available for sequence comparisons on the DCRT Convex 240. The service provided to the research community is that new zinc finger gene sequences are e-mailed to the NIH and added to the database, and a FASTA search of the results is returned without the alignments. A histogram of the statistical distribution of the search results and listing of the potential scores are included. When a match to an unpublished sequence occurs, then the name and contact information of the submitting author are returned so the concerned parties may correspond with each other. To date the collection contains 178 different entries, which is a 20% increase compared to last year. This large collection of functionally related sequences has provided an excellent problem set for multiple sequence alignment and motif analysis tests. Statistical analysis of these data have revealed 5 repeat classes of zinc finger metal bridge domains ranging in length from 27 to 32 amino acids and 22 different repeat patterns. Furthermore, compositional statistics of the largest class of domains, 29 amino acid repeat length, reveals a remarkable conservation of serine or threonine when there is an arginine or glutamine in the DNA binding region of the finger domain. A correlation between the nucleic acid sequence was established and some domains have been observed. Physical modeling of the potential DNA interaction helical regions of selected domains with a DNA helix have revealed some details of dehydration of the major groove for a sequence-specific recognition event. These studies are continuing to explore each possible DNA interaction for a selected set of finger domains.
