Disease relevance of O-PHOSPHOGLYCOLOHYDROXAMATE

• The high resolution (1.45 A) crystal structure of the Escherichia coli enzyme, encoded by the agaY gene, complexed with phosphoglycolohydroxamate (PGH) has been determined [1].

High impact information on O-PHOSPHOGLYCOLOHYDROXAMATE

• The structure of L-fuculose-1-phosphate aldolase in a cubic crystal form has been determined with and without the inhibitor phosphoglycolohydroxamate at 2.4 and 2.7 angstrom (1 angstrom = 0.1 nm) resolution, respectively [2].
• Mechanistic implications of methylglyoxal synthase complexed with phosphoglycolohydroxamic acid as observed by X-ray crystallography and NMR spectroscopy [3].
• The three-dimensional structure of the E165D mutant of the glycolytic enzyme yeast triosephosphate isomerase has been determined by X-ray diffraction at a nominal resolution of 2 A. For crystallization, the mutant enzyme was complexed with the tight-binding intermediate analog, phosphoglycolohydroxamate [4].
• The crystal structure of recombinant chicken triosephosphate isomerase (TIM, E.C. 5.3.1.1) complexed with the intermediate analogue phosphoglycolohydroxamate (PGH) has been solved by the method of molecular replacement and refined to an R-factor of 18.5% at 1.8-A resolution [5].
• Furthermore, crystals of the enzyme grown in the presence of phosphoglycolohydroxamate, a potent reaction intermediate analog, show an open active site with no inhibitor bound [6].

Biological context of O-PHOSPHOGLYCOLOHYDROXAMATE

• A competitive inhibitor of TIM, phosphoglycolohydroxamic acid (PGH) is found to be a tight binding competitive inhibitor of MGS with a K(i) of 39 nM [3].

Associations of O-PHOSPHOGLYCOLOHYDROXAMATE with other chemical compounds

• The best inhibitors of wild-type TIM are phosphoglycolohydroxamate (PGH) and 2-phosphoglycolate (2PG), with KI values of 8 microM and 26 microM, respectively [7].
• Comparison of the mode of binding of IPP and the transition state analogue phosphoglycolohydroxamate (PGH) suggests that the Glu167 side chain, as well as the triose part of the substrate, adopt different conformations as the catalysed reaction proceeds [8].

Gene context of O-PHOSPHOGLYCOLOHYDROXAMATE

• In a mother liquor containing 40 microM phosphoglycolohydroxamate (equal to 10 times the Ki of phosphoglycolohydroxamate for TIM), an inhibitor molecule binds at the active site of only that dimer of which the flexible loop is free from crystal contacts (molecule-2) [9].

Analytical, diagnostic and therapeutic context of O-PHOSPHOGLYCOLOHYDROXAMATE

• The structures of each mutant isomerase were determined from X-ray crystallography of the complex of phosphoglycolohydroxamate (PGH), an intermediate analog with the isomerase, and each was solved to a resolution of 1.9 A [10].

References