Binding site homology, enzyme

PRMTl, a nuclear receptor coactivator, exists as in a 330 kDa complex and is a H4 Arg-3 methyltransferase [133,215]. The enzyme appears to be a chromatin bound, and evidence from immunodepletion and knockout studies suggest that it is the principle, if not sole, H4 Arg-3 methyltransferase [133,215]. Mutation of the S-adenosyl methionine binding site in PRMTl annihilated its nuclear receptor coactivator activity with the androgen receptor, providing evidence for the importance of the methylation event in gene expression [215]. Yeast Rmtl, which is homologous to human PRMTl, methylates Arg-3 only in free H4 [208]. 

Application of PSSC is not limited to existing crystal structures of proteins. It could be applied to structures derived from homology models as well. A homology model, as applied for the 11 HSD types 1 and 2 enzymes performed well in the first application of PSSC for compound library design. Furthermore, it should be noted that the concept has not been developed to make predictions on structural complementarity or the appropriate orientation of functional groups in the binding site. 

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