A genomic overview of pyridoxal‐phosphate‐dependent enzymes

Enzymes that use the cofactor pyridoxal phosphate (PLP) constitute a ubiquitous class of biocatalysts. Here, we analyse their variety and genomic distribution as an example of the current opportunities and challenges for the study of protein families. In many free‐living prokaryotes, almost 1.5% of all genes code for PLP‐dependent enzymes, but in higher eukaryotes the percentage is substantially lower, consistent with these catalysts being involved mainly in basic metabolism. Assigning the function of PLP‐dependent enzymes simply on the basis of sequence criteria is not straightforward because, as a consequence of their common mechanistic features, these enzymes have intricate evolutionary relationships. Thus, many genes for PLP‐dependent enzymes remain functionally unclassified, and several of them might encode undescribed catalytic activities. In addition, PLP‐dependent enzymes often show catalytic promiscuity (that is, a single enzyme catalyses different reactions), implying that an organism can have more PLP‐dependent activities than it has genes for PLP‐dependent enzymes. This observation presumably applies to many other classes of protein‐encoding genes.

[1]  J. Jansonius,et al.  Structure, evolution and action of vitamin B6-dependent enzymes. , 1998, Current opinion in structural biology.

[2]  J. Konvalinka,et al.  Mouse brain serine racemase catalyzes specific elimination of L‐serine to pyruvate , 2003, FEBS letters.

[3]  Christopher H. Chang,et al.  Cloning, Sequencing, Heterologous Expression, Purification, and Characterization of Adenosylcobalamin-dependentd-Lysine 5,6-Aminomutase from Clostridium sticklandii * , 2000, The Journal of Biological Chemistry.

[4]  F. Studier,et al.  Structure of a yeast hypothetical protein selected by a structural genomics approach. , 2003, Acta crystallographica. Section D, Biological crystallography.

[5]  Shih-Hsiung Wu,et al.  Cloning, Sequencing, Heterologous Expression, Purification, and Characterization of Adenosylcobalamin-dependentd-Ornithine Aminomutase from Clostridium sticklandii * , 2001, The Journal of Biological Chemistry.

[6]  Annabel E. Todd,et al.  From structure to function: Approaches and limitations , 2000, Nature Structural Biology.

[7]  J. de Miranda,et al.  Human serine racemase: moleular cloning, genomic organization and functional analysis. , 2000, Gene.

[8]  P. Christen,et al.  From cofactor to enzymes. The molecular evolution of pyridoxal-5'-phosphate-dependent enzymes. , 2001, Chemical record.

[9]  G. O’Toole,et al.  CobD, a Novel Enzyme withl-Threonine-O-3-phosphate Decarboxylase Activity, Is Responsible for the Synthesis of (R)-1-Amino-2-propanol O-2-Phosphate, a Proposed New Intermediate in Cobalamin Biosynthesis inSalmonella typhimurium LT2* , 1998, The Journal of Biological Chemistry.

[10]  Jeffrey P. Jones,et al.  Alternative splicing determines the function of CYP4F3 by switching substrate specificity. , 2001, The Journal of biological chemistry.

[11]  N. Grishin,et al.  Modeling of the spatial structure of eukaryotic ornithine decarboxylases , 1995, Protein science : a publication of the Protein Society.

[12]  D. Herschlag,et al.  Catalytic promiscuity and the evolution of new enzymatic activities. , 1999, Chemistry & biology.

[13]  G. Schneider,et al.  The manifold of vitamin B6 dependent enzymes. , 2000, Structure.

[14]  D. Gottlieb,et al.  Developmentally regulated expression of an exon containing a stop codon in the gene for glutamic acid decarboxylase. , 1990, Proceedings of the National Academy of Sciences of the United States of America.

[15]  Q. Han,et al.  Kynurenine aminotransferase and glutamine transaminase K of Escherichia coli: identity with aspartate aminotransferase. , 2001, The Biochemical journal.

[16]  S. Copley.  Enzymes with extra talents: moonlighting functions and catalytic promiscuity. , 2003, Current opinion in chemical biology.

[17]  P Christen,et al.  The molecular evolution of pyridoxal-5'-phosphate-dependent enzymes. , 2000, Advances in enzymology and related areas of molecular biology.

[18]  Arthur J. L. Cooper,et al.  Toxic, halogenated cysteine S-conjugates and targeting of mitochondrial enzymes of energy metabolism. , 2002, Biochemical pharmacology.

[19]  B. Graveley.  Alternative splicing: increasing diversity in the proteomic world. , 2001, Trends in genetics : TIG.

[20]  K N Sheth,et al.  Purification of serine racemase: biosynthesis of the neuromodulator D-serine. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[21]  T. Clausen,et al.  Crystal structure of cystalysin from Treponema denticola: a pyridoxal 5′‐phosphate‐dependent protein acting as a haemolytic enzyme , 2000, The EMBO journal.

[22]  D. Thiel,et al.  Lack of catalytic activity of a murine mRNA cytoplasmic serine hydroxymethyltransferase splice variant: evidence against alternative splicing as a regulatory mechanism. , 2001, Biochemistry.

[23]  H. Fukamachi,et al.  Cloning and characterization of the L-cysteine desulfhydrase gene of Fusobacterium nucleatum. , 2002, FEMS microbiology letters.

[24]  P. Plateau,et al.  Role of d-Cysteine Desulfhydrase in the Adaptation of Escherichia coli to d-Cysteine* , 2001, The Journal of Biological Chemistry.

[25]  R. John,et al.  Pyridoxal phosphate-dependent enzymes. , 1995, Biochimica et biophysica acta.

[26]  G. Bourenkov,et al.  X‐ray structure of MalY from Escherichia coli: a pyridoxal 5′‐phosphate‐dependent enzyme acting as a modulator in mal gene expression , 2000, EMBO Journal.

[27]  G Capitani,et al.  The human cDNA for a homologue of the plant enzyme 1-aminocyclopropane-1-carboxylate synthase encodes a protein lacking that activity. , 2001, Gene.

[28]  B. Rost.  Enzyme function less conserved than anticipated. , 2002, Journal of molecular biology.