Amino acid residues of huEPO and huEPOR that contact each other in site 1 and site 2 intermolecular contact areas, and the corresponding residues in xlEPO.

axlEPO residues corresponding to right-hand “huEPO residues” [21]. Amino acid residues that are identical to huEPO residues are in bold.bBuried residues (>5.0 Å2) of huEPO in site 1 and site 2 intermolecular contact areas [30]. Available mutagenesis information [26–29] are highlighted according to the maximal degree of loss of in vitro bioactivity: bold underlined, >50-fold; bold, >5-fold; underlined, 2–5-fold; not highlighted, no effect.cHuEPOR residues within 4.5-Å distance from huEPO in the crystal structure of human EPO-(EPOR)2 complex (Protein Data Bank accession number, 1EER) [30]. Amino acid residues that are conserved in X. laevis are in bold [49].dAmino acid residues of huEPO and huEPOR that form interactions with each other, such as hydrogen bond and hydrophobic binding, are in italics [30].eAmino acid residues of xlEPOR that conserved in huEPOR[49].huEPO, human erythropoietin; huEPOR, human EPO receptor; xlEPO, X. laevis EPO.Amino acid residues of huEPO and huEPOR that contact each other in site 1 and site 2 intermolecular contact areas, and the corresponding residues in xlEPO.