Convergent evolution sheds light on the anti-beta-elimination mechanism common to family 1 and 10 polysaccharide lyases

Charnock, Simon, Black, Gary, Brown, Ian E., Turkenburg, Johan and Davies, Gideon (2002) Convergent evolution sheds light on the anti-beta-elimination mechanism common to family 1 and 10 polysaccharide lyases. Proceedings of the National Academy of Sciences of the United States of America, 99 (19). pp. 12067-12072. ISSN 0027-8424

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Enzyme-catalyzed β-elimination of sugar uronic acids, exemplified by the degradation of plant cell wall pectins, plays an important role in a wide spectrum of biological processes ranging from the recycling of plant biomass through to pathogen virulence. The three-dimensional crystal structure of the catalytic module of a “family PL-10” polysaccharide lyase, Pel10Acm from Cellvibrio japonicus, solved at a resolution of 1.3 Å, reveals a new polysaccharide lyase fold and is the first example of a polygalacturonic acid lyase that does not exhibit the “parallel β-helix” topology. The “Michaelis” complex of an inactive mutant in association with the substrate trigalacturonate/Ca2+ reveals the catalytic machinery harnessed by this polygalacturonate lyase, which displays a stunning resemblance, presumably through convergent evolution, to the tetragalacturonic acid complex observed for a structurally unrelated polygalacturonate lyase from family PL-1. Common coordination of the −1 and +1 subsite saccharide carboxylate groups by a protein-liganded Ca2+ ion, the positioning of an arginine catalytic base in close proximity to the α-carbon hydrogen and numerous other conserved enzyme–substrate interactions, considered in light of mutagenesis data for both families, suggest a generic polysaccharide anti-β-elimination mechanism.

Item Type: Article
Additional Information: Devised and supervised part of the experimental work and co-wrote the paper. Research showed that the six active-centre groups of two structurally unrelated lyases are essentially in identical positions (an example of convergent evolution). Invited lecture International Workshop on Molecular, Biochemical, Structural and Genetic Aspects of Carbohydrate-Modifying Enzymes, Ireland (2003)
Subjects: A100 Pre-clinical Medicine
Department: Faculties > Health and Life Sciences > Applied Sciences
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Depositing User: EPrint Services
Date Deposited: 07 May 2008 14:15
Last Modified: 12 Oct 2019 17:29

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