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Journal of Bacteriology, June 2006, p. 4542-4552, Vol. 188, No. 12
0021-9193/06/$08.00+0     doi:10.1128/JB.00122-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Crystal Structure of Pyridoxal Kinase from the Escherichia coli pdxK Gene: Implications for the Classification of Pyridoxal Kinases

Martin K. Safo,1* Faik N. Musayev,1 Martino L. di Salvo,2 Sharyn Hunt,1 Jean-Baptiste Claude,3 and Verne Schirch1

Department of Medicinal Chemistry and Institute for Structural Biology and Drug Discovery, Virginia Commonwealth University, Richmond, Virginia 23219,1 Dipartimento di Scienze Biochimiche A. Rossi Fanelli, Università La Sapienza, 00185 Roma, Italy,2 Information Génomique and Structurale (UPR CNRS 2589), 163 Avenue de Luminy, Case 934, 13288 Marseille Cedex 9, France3

Received 23 January 2006/ Accepted 22 March 2006

The pdxK and pdxY genes have been found to code for pyridoxal kinases, enzymes involved in the pyridoxal phosphate salvage pathway. Two pyridoxal kinase structures have recently been published, including Escherichia coli pyridoxal kinase 2 (ePL kinase 2) and sheep pyridoxal kinase, products of the pdxY and pdxK genes, respectively. We now report the crystal structure of E. coli pyridoxal kinase 1 (ePL kinase 1), encoded by a pdxK gene, and an isoform of ePL kinase 2. The structures were determined in the unliganded and binary complexes with either MgATP or pyridoxal to 2.1-, 2.6-, and 3.2-Å resolutions, respectively. The active site of ePL kinase 1 does not show significant conformational change upon binding of either pyridoxal or MgATP. Like sheep PL kinase, ePL kinase 1 exhibits a sequential random mechanism. Unlike sheep pyridoxal kinase, ePL kinase 1 may not tolerate wide variation in the size and chemical nature of the 4' substituent on the substrate. This is the result of differences in a key residue at position 59 on a loop (loop II) that partially forms the active site. Residue 59, which is His in ePL kinase 1, interacts with the formyl group at C-4' of pyridoxal and may also determine if residues from another loop (loop I) can fill the active site in the absence of the substrate. Both loop I and loop II are suggested to play significant roles in the functions of PL kinases.

* Corresponding author. Mailing address: Department of Medicinal Chemistry and Institute for Structural Biology and Drug Discovery, 800 E. Leigh St., Virginia Commonwealth University, Richmond, VA 23219. Phone: (804) 828-7291. Fax: (804) 827-3664. E-mail: msafo{at}mail2.vcu.edu.

Journal of Bacteriology, June 2006, p. 4542-4552, Vol. 188, No. 12
0021-9193/06/$08.00+0     doi:10.1128/JB.00122-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.





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