The invention relates generally to a modified human C3 protein containing a number of single amino acid changes in the α and β-chain of human C3 protein, designed to increase the affinity of the modified protein to factor B or Bb, to decrease the affinity of the modified protein to factor H, and to reduce the immunogenicity of the modified protein as compared to the native human C3 protein, a nucleotide sequence encoding the modified C3 protein, a plasmid or viral vector containing the nucleotide sequence for expression the modified C3 protein, and a host cell containing the plasmid or viral vector. We also present a polyethylene glycol covalently bound to the modified C3 protein for reducing immunogenicity and increasing plasma half-life of the modified C3 protein; a method for depleting complement in a patient by administering the modified C3 protein to the patient in an amount effective to deplete complement; a method of ameliorating effects caused by or disease or a method of ameliorating reperfusion injury in a patient by delivering the modified C3 protein.