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Computational insig...
Computational insights into the mechanism of porphobilinogen synthase
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- Erdtman, Edvin (author)
- Örebro universitet,Akademin för naturvetenskap och teknik,Biofysikalisk kemi,Örebro universitet, Akademin för naturvetenskap och teknik
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- Bushnell, Eric A. C. (author)
- Department of Chemistry and Biochemistry, University of Windsor, Windsor ON, Canada
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- Gauld, James W. (author)
- Department of Chemistry and Biochemistry, University of Windsor, Windsor ON, Canada
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- Eriksson, Leif A. (author)
- School of Chemistry, National University Ireland (NUI) Galway, Galway, Ireland
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(creator_code:org_t)
- 2010-11-23
- 2010
- English.
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In: Journal of Physical Chemistry B. - Washington : American Chemical Society (ACS). - 1520-6106 .- 1520-5207. ; 114:50, s. 16860-16870
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Abstract
Subject headings
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- 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 intersubstrateC-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 ratelimiting barrier (17.5 kcal/mol) that is lower than those in which the intersubstrate C-C bond is formed first (22.8 kcal/mol).
Subject headings
- NATURVETENSKAP -- Kemi -- Fysikalisk kemi (hsv//swe)
- NATURAL SCIENCES -- Chemical Sciences -- Physical Chemistry (hsv//eng)
Keyword
- NATURAL SCIENCES
- NATURVETENSKAP
- Physical chemistry
- Fysikalisk kemi
- Biophysical chemistry
- Biofysikalisk kemi
- Biochemistry
- Biokemi
Publication and Content Type
- ref (subject category)
- art (subject category)
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