Tetrapyrrole assembly and modification into the ligands of biologically functional cofactors.
Data obtained using a combination of molecular biology and NMR spectroscopy has transformed our thinking about the evolution of the biochemical machinery required for the synthesis of the vital metallopigments: haem, chlorophyll, vitamin B12 and factor F430. One of the most recent advances is the discovery of a unique dipyrromethane cofactor that is bound covalently at the active site of porphobillinogen deaminase, the key enzyme of tetrapyrrole assembly. We will also discuss how the oxidation level and chromophoric arrangement of the uroporphinoid ring, rather than its substitution pattern, provides the necessary molecular recognition for some of the later enzymes, whose function is to decorate the template by C-methylation on the way to the biologically active cofactors.
Warren
M J
MJ
Department of Chemistry, Texas A and M University, College Station 77843-3255.
Scott
A I
AI
D001665:Binding Sites; D011163:Hydroxymethylbilane Synthase / Q000737:chemistry; D008024:Ligands; D008745:Methylation; D011162:Porphobilinogen / Q000737:chemistry; D011758:Pyrroles / Q000737:chemistry*; D045725:Tetrapyrroles; D014577:Uroporphyrinogens / Q000737:chemistry* / Q000378:metabolism
D008024:Ligands; D011758:Pyrroles; D045725:Tetrapyrroles; D014577:Uroporphyrinogens; C056776:dipyrromethane cofactor; D011162:Porphobilinogen; D011163:Hydroxymethylbilane Synthase