DRE-antagonist modulator (DREM)

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The downstream regulatory element (DRE) is known to silence transcription of the prodynorphin and c-fos genes. DRE-antagonistist modulator (DREAM) binds to DRE in the apo-form, probably as a homotetramer. "Upon stimulation by Ca2+, DREAM's ability to bind to the DRE and its repressor function are prevented." [24]. DREM is 284 residues long and contains four EF-hands. The 110 residues preceding the first EF-hand may be responsible for binding to DNA; however, no homolog is recognized. The first and second EF-hands have unusual distributions of potential Ca2+ binding ligands - X, Y, Z, -X, -Z Asn, Cys, Thr, Asp, Thr and Asp, Asp, Asn, His, Asp. In proteins Ca2+ is usually coordinated by O; the S of Cys and the N of His may coordinate water which in turn binds Ca2+. The third and fourth EF-hands appear to bind calcium.