Structural basis of pyrrole polymerization in human porphobilinogen deaminase

• Published in: Biochimica et biophysica acta. General subjects Vol. 1862; no. 9; pp. 1948 - 1955
• Main Authors: Pluta, Paula, Roversi, Pietro, Bernardo-Seisdedos, Ganeko, Rojas, Adriana L., Cooper, Jonathan B., Gu, Shuang, Pickersgill, Richard W., Millet, Oscar
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.09.2018
• Subjects: active sites; Acute intermittent porphyria; Catalysis; catalytic activity; Catalytic Domain; crystal structure; Crystallography, X-Ray; Enzyme mechanism; heme; Heme biosynthesis; Human porphobilinogen deaminase (PBGD); Humans; Hydroxymethylbilane Synthase - chemistry; Hydroxymethylbilane Synthase - metabolism; missense mutation; nuclear magnetic resonance spectroscopy; Polymerization; porphobilinogen; Porphobilinogen - chemistry; Porphobilinogen - metabolism; porphyria; Protein Conformation; pyrroles; Pyrroles - chemistry; Pyrroles - metabolism; Reaction intermediates; Uroporphyrinogens - chemistry; Uroporphyrinogens - metabolism; X-ray structure; Reaction intermediates; Enzyme mechanism; Heme biosynthesis; Human porphobilinogen deaminase (PBGD); X-ray structure; Acute intermittent porphyria

Human porphobilinogen deaminase (PBGD), the third enzyme in the heme pathway, catalyzes four times a single reaction to convert porphobilinogen into hydroxymethylbilane. Remarkably, PBGD employs a single active site during the process, with a distinct yet chemically equivalent bond formed each time....