A novel α-N-acetylgalactosaminidase family with an NAD +-dependent catalytic mechanism suitable for enzymatic removal of blood group A antigens

Gerlind Sulzenbacher; Qiyong Peter Liu; Eric P. Bennett; Steven B. Levery; Yves Bourne; Guillaume Ponchel; Henrik Clausen; Bernard Henrissat

doi:10.3109/10242420903424259

A novel α-N-acetylgalactosaminidase family with an NAD ⁺-dependent catalytic mechanism suitable for enzymatic removal of blood group A antigens

Gerlind Sulzenbacher^*, Qiyong Peter Liu, Eric P. Bennett, Steven B. Levery, Yves Bourne, Guillaume Ponchel, Henrik Clausen, Bernard Henrissat

^*Corresponding author for this work

3 Citations (Scopus)

Abstract

Enzymatic removal of blood group A and B antigens from the surface of red blood cells to develop universal blood was a pioneering vision originally proposed more than 25 years ago. A great variety of enzymes, potentially suitable for enzymatic conversion of red blood cells, has been described since, but the process has not been economically viable because of the poor kinetic properties and low pH optimum of enzymes. Recently, the identification of two new families of bacterial glycosidases with enhanced kinetic properties for the removal of A and B antigens at neutral pH marked a milestone in the field of transfusion medicine (Liu et al. 2007). Here we present a detailed structural analysis of Elizabethkingia meningosepticum a-N-acetylgalactosaminidase (NagA) shown to efficiently cleave the A antigen. NagA, a member of glycoside hydrolase (GH) family 109, employs an unusual catalytic mechanism involving NAD ⁺. Comparison of the active-center structure with that of members of GH family 4 reveals a striking degree of structural similarity that allows the postulation of a common reaction mechanism and illustrates a beautiful example of convergent evolution.

Original language	English
Journal	Biocatalysis and Biotransformation
Volume	28
Issue number	1
Pages (from-to)	22-32
Number of pages	11
ISSN	1024-2422
DOIs	https://doi.org/10.3109/10242420903424259
Publication status	Published - 1 Jan 2010

Keywords

ABO blood group system
Blood group antigens
Crystal structure
Enzymatic conversion
GH109
GH4

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A novel α-N-acetylgalactosaminidase family with an NAD ⁺-dependent catalytic mechanism suitable for enzymatic removal of blood group A antigens. / Sulzenbacher, Gerlind; Liu, Qiyong Peter; Bennett, Eric P. et al.

In: Biocatalysis and Biotransformation, Vol. 28, No. 1, 01.01.2010, p. 22-32.

Research output: Contribution to journal › Journal article › Research › peer-review

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abstract = "Enzymatic removal of blood group A and B antigens from the surface of red blood cells to develop universal blood was a pioneering vision originally proposed more than 25 years ago. A great variety of enzymes, potentially suitable for enzymatic conversion of red blood cells, has been described since, but the process has not been economically viable because of the poor kinetic properties and low pH optimum of enzymes. Recently, the identification of two new families of bacterial glycosidases with enhanced kinetic properties for the removal of A and B antigens at neutral pH marked a milestone in the field of transfusion medicine (Liu et al. 2007). Here we present a detailed structural analysis of Elizabethkingia meningosepticum a-N-acetylgalactosaminidase (NagA) shown to efficiently cleave the A antigen. NagA, a member of glycoside hydrolase (GH) family 109, employs an unusual catalytic mechanism involving NAD +. Comparison of the active-center structure with that of members of GH family 4 reveals a striking degree of structural similarity that allows the postulation of a common reaction mechanism and illustrates a beautiful example of convergent evolution.",

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AU - Levery, Steven B.

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AU - Ponchel, Guillaume

AU - Clausen, Henrik

AU - Henrissat, Bernard

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AB - Enzymatic removal of blood group A and B antigens from the surface of red blood cells to develop universal blood was a pioneering vision originally proposed more than 25 years ago. A great variety of enzymes, potentially suitable for enzymatic conversion of red blood cells, has been described since, but the process has not been economically viable because of the poor kinetic properties and low pH optimum of enzymes. Recently, the identification of two new families of bacterial glycosidases with enhanced kinetic properties for the removal of A and B antigens at neutral pH marked a milestone in the field of transfusion medicine (Liu et al. 2007). Here we present a detailed structural analysis of Elizabethkingia meningosepticum a-N-acetylgalactosaminidase (NagA) shown to efficiently cleave the A antigen. NagA, a member of glycoside hydrolase (GH) family 109, employs an unusual catalytic mechanism involving NAD +. Comparison of the active-center structure with that of members of GH family 4 reveals a striking degree of structural similarity that allows the postulation of a common reaction mechanism and illustrates a beautiful example of convergent evolution.

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A novel α-N-acetylgalactosaminidase family with an NAD ⁺-dependent catalytic mechanism suitable for enzymatic removal of blood group A antigens

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