ACE2, the first known human homologue of angiotensin-converting enzyme (ACE), was identified from 5' sequencing of a human heart failure ventricle cDNA library. ACE2 has an apparent signal peptide, a single metalloprotease active site, and a transmembrane domain. The metalloprotease catalytic domains of ACE2 and ACE are 42% identical, and comparison of the genomic structures indicates that the two genes arose through duplication. In contrast to the more ubiquitous ACE, ACE2 transcripts are found only in heart, kidney, and testis of 23 human tissues examined. Immunohistochemistry shows ACE2 protein predominantly in the endothelium of coronary and intrarenal vessels and in renal tubular epithelium. Active ACE2 enzyme is secreted from transfected cells by cleavage N-terminal to the transmembrane domain. Recombinant ACE2 hydrolyzes the carboxy terminal leucine from angiotensin I to generate angiotensin 1-9, which is converted to smaller angiotensin peptides by ACE in vitro and by cardiomyocytes in culture. ACE2 can also cleave des-Arg bradykinin and neurotensin but not bradykinin or 15 other vasoactive and hormonal peptides tested. ACE2 is not inhibited by lisinopril or captopril. The organ- and cell-specific expression of ACE2 and its unique cleavage of key vasoactive peptides suggest an essential role for ACE2 in the local renin-angiotensin system of the heart and kidney. The full text of this article is available at http://www. circresaha.org.

A cDNA corresponding to a thiol-specifc antioxidant enzyme (TSA) was isolated from a rat brain cDNA library with the use of antibodies to bovine TSA.

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A major mode of gene regulation occurs via the binding of speci®c proteins to speci®c DNA sequences. The availability of complete bacterial genome sequences offers an unprecedented opportunity to describe networks of such interactions by correlating existing experimental data with computational predictions. Of the 240 candidate Escherichia coli DNAbinding proteins, about 55 have DNA-binding sites identi®ed by DNA footprinting. We used these sites to construct recognition matrices, which we used to search for additional binding sites in the E. coli genomic sequence. Many of these matrices show a strong preference for non-coding DNA. Discrepancies are identi®ed between matrices derived from natural sites and those derived from SELEX (Systematic Evolution of Ligands by Exponential enrichment) experiments. We have constructed a database of these proteins and binding sites, called DPInteract (available at