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Crystal structure of a trimeric form of dephosphocoenzyme A kinase from Escherichia coli
Author(s) -
O'Toole Nicholas,
Barbosa João A.R.G.,
Li Yunge,
Hung LiWei,
Matte Allan,
Cygler Miroslaw
Publication year - 2003
Publication title -
protein science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.353
H-Index - 175
eISSN - 1469-896X
pISSN - 0961-8368
DOI - 10.1110/ps.0227803
Subject(s) - trimer , escherichia coli , biochemistry , nucleoside triphosphate , nucleotide , enzyme , sequence alignment , binding site , peptide sequence , biology , protein structure , active site , chemistry , conserved sequence , sequence motif , stereochemistry , dna , gene , dimer , organic chemistry
Coenzyme A (CoA) is an essential cofactor used in a wide variety of biochemical pathways. The final step in the biosynthesis of CoA is catalyzed by dephosphocoenzyme A kinase (DPCK, E.C. 2.7.1.24). Here we report the crystal structure of DPCK from Escherichia coli at 1.8 Å resolution. This enzyme forms a tightly packed trimer in its crystal state, in contrast to its observed monomeric structure in solution and to the monomeric, homologous DPCK structure from Haemophilus influenzae . We have confirmed the existence of the trimeric form of the enzyme in solution using gel filtration chromatography measurements. Dephospho‐CoA kinase is structurally similar to many nucleoside kinases and other P‐loop‐containing nucleotide triphosphate hydrolases, despite having negligible sequence similarity to these enzymes. Each monomer consists of five parallel β‐strands flanked by α‐helices, with an ATP‐binding site formed by a P‐loop motif. Orthologs of the E. coli DPCK sequence exist in a wide range of organisms, including humans. Multiple alignment of orthologous DPCK sequences reveals a set of highly conserved residues in the vicinity of the nucleotide/CoA binding site.