Related Experiment Video
Updated: Jun 6, 2026

Isotopic Effect in Double Proton Transfer Process of Porphycene Investigated by Enhanced QM/MM Method
Published on: July 19, 2019
Computational insights into the mechanism of porphobilinogen synthase
Edvin Erdtman1, Eric A C Bushnell, James W Gauld
1School of Science and Technology, Örebro Life Science Center, Örebro University, Örebro, Sweden.
Abstract:
Porphobilinogen synthase (PBGS) is a key enzyme in heme biosynthesis that catalyzes the formation of porphobilinogen (PBG) from two 5-aminolevulinic acid (5-ALA) molecules via formation of intersubstrate C-N and C-C bonds. The active site consists of several invariant residues, including two lysyl residues (Lys210 and Lys263; yeast numbering) that bind the two substrate moieties as Schiff bases. Based on experimental studies, various reaction mechanisms have been proposed for this enzyme that generally can be classified according to whether the intersubstrate C-C or C-N bond is formed first. However, the detailed catalytic mechanism of PBGS remains unclear. In the present study, we have employed density functional theory methods in combination with chemical models of the two key lysyl residues and two substrate moieties in order to investigate various proposed reaction steps and gain insight into the mechanism of PBGS. Importantly, it is found that mechanisms in which the intersubstrate C-N bond is formed first have a rate-limiting barrier (17.5 kcal/mol) that is lower than those in which the intersubstrate C-C bond is formed first (22.8 kcal/mol).
Related Concept Videos
Structure of Porins
ATP Synthase: Mechanism
Porin Insertion in the Outer Mitochondrial Membrane
Three models describe the assembly of porins by the SAM complex and their insertion into the outer membrane. Model 1 suggests that porins are assembled outside the SAM channel as the...
Gene Families
Occasionally these regions can be adapted to take on new roles within the organism, becoming novel genes...
Covalently Linked Protein Regulators
These groups modify specific amino acids in a protein.
Electron Transport Chain: Complex III and IV

