Sökning: WFRF:(Kamerlin Shina C. Lynn 1981 ) >
Computer simulation...
Computer simulations of the catalytic mechanism of wild-type and mutant beta-phosphoglucomutase
-
- Barrozo, Alexandre (författare)
- Uppsala universitet,Science for Life Laboratory, SciLifeLab,Institutionen för cell- och molekylärbiologi
-
- Liao, Qinghua (författare)
- Uppsala universitet,Strukturbiologi,Science for Life Laboratory, SciLifeLab
-
- Esguerra, Mauricio (författare)
- Uppsala universitet,Beräkningsbiologi och bioinformatik,Science for Life Laboratory, SciLifeLab
-
visa fler...
-
- Marloie, Gael (författare)
- Uppsala universitet,Science for Life Laboratory, SciLifeLab,Institutionen för cell- och molekylärbiologi
-
- Florian, Jan (författare)
- Loyola Univ Chicago, Dept Chem & Biochem, Chicago, IL 60660 USA.
-
- Williams, Nicholas H. (författare)
- Univ Sheffield, Dept Chem, Sheffield S3 7HF, S Yorkshire, England.
-
- Kamerlin, Shina C. Lynn, 1981- (författare)
- Uppsala universitet,Institutionen för cell- och molekylärbiologi,Science for Life Laboratory, SciLifeLab
-
visa färre...
-
(creator_code:org_t)
- 2018
- 2018
- Engelska.
-
Ingår i: Organic and biomolecular chemistry. - : Royal Society of Chemistry. - 1477-0520 .- 1477-0539. ; 16:12, s. 2060-2073
- Relaterad länk:
-
https://doi.org/10.1...
-
visa fler...
-
https://uu.diva-port... (primary) (Raw object)
-
https://pubs.rsc.org...
-
https://urn.kb.se/re...
-
https://doi.org/10.1...
-
visa färre...
Abstract
Ämnesord
Stäng
- beta-Phosphoglucomutase (beta-PGM) has served as an important model system for understanding biological phosphoryl transfer. This enzyme catalyzes the isomerization of beta-glucose-1-phosphate to -glucose-6-phosphate in a two-step process proceeding via a bisphosphate intermediate. The conventionally accepted mechanism is that both steps are concerted processes involving acid-base catalysis from a nearby aspartate (D10) side chain. This argument is supported by the observation that mutation of D10 leaves the enzyme with no detectable activity. However, computational studies have suggested that a substrate-assisted mechanism is viable for many phosphotransferases. Therefore, we carried out empirical valence bond (EVB) simulations to address the plausibility of this mechanistic alternative, including its role in the abolished catalytic activity of the D10S, D10C and D10N point mutants of beta-PGM. In addition, we considered both of these mechanisms when performing EVB calculations of the catalysis of the wild type (WT), H20A, H20Q, T16P, K76A, D170A and E169A/D170A protein variants. Our calculated activation free energies confirm that D10 is likely to serve as the general base/acid for the reaction catalyzed by the WT enzyme and all its variants, in which D10 is not chemically altered. Our calculations also suggest that D10 plays a dual role in structural organization and maintaining electrostatic balance in the active site. The correct positioning of this residue in a catalytically competent conformation is provided by a functionally important conformational change in this enzyme and by the extensive network of H-bonding interactions that appear to be exquisitely preorganized for the transition state stabilization.
Ämnesord
- NATURVETENSKAP -- Biologi -- Biokemi och molekylärbiologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences -- Biochemistry and Molecular Biology (hsv//eng)
- NATURVETENSKAP -- Kemi -- Organisk kemi (hsv//swe)
- NATURAL SCIENCES -- Chemical Sciences -- Organic Chemistry (hsv//eng)
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
Hitta via bibliotek
Till lärosätets databas