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J. Biol. Chem., Vol. 279, Issue 35, 37185-37190, August 27, 2004

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Cofactor-independent Phosphoglycerate Mutase Has an Essential Role in Caenorhabditis elegans and Is Conserved in Parasitic Nematodes^*

Yinhua Zhang, Jeremy M. Foster, Sanjay Kumar, Marjorie Fougere, and Clotilde K. S. Carlow

From the New England Biolabs, Beverly, Massachusetts 01915

Phosphoglycerate mutases catalyze the interconversion of 2- and 3-phosphoglycerate in the glycolytic and gluconeogenic pathways. They exist in two unrelated forms that are either cofactor (2,3-diphosphoglycerate)-dependent or cofactor-independent. The two enzymes have no similarity in amino acid sequence, tertiary structure, or catalytic mechanism. Certain organisms including vertebrates have only the cofactor-dependent form, whereas other organisms can possess the independent form or both. Caenorhabditis elegans has been predicted to have only independent phosphoglycerate mutase. In this study, we have cloned and produced recombinant, independent phosphoglycerate mutases from C. elegans and the human-parasitic nematode Brugia malayi. They are 70% identical to each other and related to known bacterial, fungal, and protozoan enzymes. The nematode enzymes possess the catalytic serine, and other key amino acids proposed for catalysis and recombinant enzymes showed typical phosphoglycerate mutase activities in both the glycolytic and gluconeogenic directions. The gene is essential in C. elegans, because the reduction of its activity by RNA interference led to embryonic lethality, larval lethality, and abnormal body morphology. Promoter reporter analysis indicated widespread expression in larval and adult C. elegans with the highest levels apparent in the nerve ring, intestine, and body wall muscles. The enzyme was found in a diverse group of nematodes representing the major clades, indicating that it is conserved throughout this phylum. Our results demonstrate that nematodes, unlike vertebrates, utilize independent phosphoglycerate mutase in glycolytic and gluconeogenic pathways and that the enzyme is probably essential for all nematodes.

Received for publication, May 26, 2004 , and in revised form, July 2, 2004.

^* This work was supported by Donald Comb (New England Biolabs). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

To whom correspondence should be addressed: New England Biolabs, 32 Tozer Road, Beverly, MA 01915. Tel.: 978-927-5054 (ext. 263); Fax: 978-921-1350; E-mail: carlow{at}neb.com.

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