Homologous sequences in steroidogenic enzymes, steroid receptors and a steroid binding protein suggest a consensus steroid-binding sequence.
The amino acid sequences of two steroidogenic enzymes, P450c17 (steroid 17 alpha-hydroxylase/17,20 lyse) and P450c21 (steroid 21-hydroxylase), are only 28.9% identical. However, these proteins share a region of 21 amino acids bearing 17 identical residues, which we previously suggested may represent the steroid binding site. We assembled a sequence database of known steroid-binding proteins and searched this with the sequence of this 21 amino acid region. The steroidogenic enzymes, P450c17, P450c21, P450scc (the cholesterol side-chain cleavage enzyme), and P450c11 (steroid 11 beta/18-hydroxylase) share a subregion of 17 amino acids having at least 15 identical residues. Related sequences were identified in a computerized search of the available sequences of steroid hormone receptors and binding proteins. These sequences were invariably found within larger domains previously associated with steroid binding. From these we propose a more general consensus sequence of LPLLL +/- 000KDRE0LKRL +/- PV, where +/- refers to any charged amino acid, and 0 refers to an uncharged amino acid. This consensus sequence predicts 147 or 187 total amino acids in 11 human proteins examined (78.6%). An equivalent degree of sequence identity, 178 of 221 amino acids (80.5%) was found among 13 animal homologs of these human proteins. The ability of this consensus sequence to predict 325 of 408 amino acids (79.7%) strongly suggests this sequence is necessary, if not sufficient, for a steroid binding site in many proteins. Lecithin-cholesterol acetyl transferase, cholesterol ester transfer protein, and steroid sulfatase did not have sequences similar to our consensus sequence.
Picado-Leonard
J
J
Department of Pediatrics, University of California, San Francisco 94143.
Miller
W L
WL
D000595:Amino Acid Sequence; D000818:Animals; D002352:Carrier Proteins / Q000032:analysis / Q000235:genetics*; D006801:Humans; D008969:Molecular Sequence Data; D011987:Receptors, Steroid / Q000235:genetics* / Q000378:metabolism; D012689:Sequence Homology, Nucleic Acid; D013254:Steroid 17-alpha-Hydroxylase / Q000032:analysis / Q000235:genetics*; D013255:Steroid 21-Hydroxylase / Q000032:analysis / Q000235:genetics*; D013250:Steroid Hydroxylases / Q000235:genetics*; D013256:Steroids / Q000378:metabolism*
D002352:Carrier Proteins; D011987:Receptors, Steroid; D013256:Steroids; D013250:Steroid Hydroxylases; D013255:Steroid 21-Hydroxylase; D013254:Steroid 17-alpha-Hydroxylase