Critical role of human bisphosphoglycerate mutase Cys22 in the phosphatase activator-binding site.

The Journal of Biological Chemistry
P RavelM C Garel

Abstract

The enzymatic activities catalyzed by bisphosphoglycerate mutase (BPGM, EC 5.4.2.4) have been shown to occur at a unique active site, with distinct binding sites for diphosphoglycerates and monophosphoglycerates. The physiological phosphatase activator (2-phosphoglycolate) binds to BPGM at an undetermined site. BPGM variants were constructed by site-directed mutagenesis of three amino acid residues in the active site to identify residues specifically involved in the binding of the monophosphoglycerates and 2-phosphoglycolate. Substitution of Cys22 by functionally conservative residues, Thr or Ser, caused a great decrease in 2-phosphoglycolate-stimulated phosphatase activity and in the Ka value of the activator, whereas it caused no change in other catalytic activities or in the Km values of 2,3-diphosphoglycerate (2,3-DPG) and glycerate 3-phosphate (3-PG, EC 1.1.1.12), indicating that Cys22 is specifically involved either directly or indirectly in 2-phosphoglycolate binding. Kinetic experiments showed that the Ka of the cofactor and the Km of 3-PG were affected by the substitution of Ser23 indicating that this residue is necessary for the fixation of both 3-PG and 2-phosphoglycolate. The R89K variant has previously been shown t...Continue Reading

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Citations

Nov 5, 2013·Spectrochimica Acta. Part A, Molecular and Biomolecular Spectroscopy·Samreen AmaniAabgeena Naeem
Nov 4, 2010·Acta Crystallographica. Section F, Structural Biology and Crystallization Communications·A PattersonJ Nairn
Aug 18, 2016·Journal of Structural and Functional Genomics·Yoichi MurakamiKengo Kinoshita
Jul 20, 2004·The Journal of Biological Chemistry·Yanli WangWeimin Gong
Jun 19, 1998·Biochemistry·A N Szilágyi, M Vas

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