Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:4.1.2.13 (aldolase)
 3,461 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The inactivation of Streptococcus faecalis by radiolytically generated selective inorganic radical anions was investigated. The Br-2 radical, but not (CNS)-2, had a pronounced radiosensitizing action. In gamma-irradiated solutions at pH 7.0, the radiosensitization of a variety of scavenging systems was studied. Among these the D10 for N2/Br- was 0.082 kGy while N2O/CNS- = 0.35 kGy, N2O = 0.25 kGy, N2 = 0.47, and O2 = 0.16 kGy. As shown previously, inactivation in N2O/Br- systems is due mainly to Br2 and HOBr. From the variation of the inactivation with pH by Br-2 and (CNS)-2 it was deduced that tyrosine is crucial for the survival of S. faecalis via inactivation of enzymes with essential tyrosine residues such as aldolase and lipoyl dehydrogenase which are presumably needed to make energy available for DNA repair. Studies with a variety of scavengers also revealed that the t-butanol radical produced some radiosensitization of S. faecalis while the damaging effect of e-aq was much less than OH as shown by the D10 at pH 7.0; N2/t-butanol = 0.32 and N2/ethanol = 0.71. The radiosensitizing action of Br-2 in a natural environment containing sewage sludge was also determined, using the faecal streptococcal group as test organisms.
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PMID:Radiosensitization of microorganisms by radical anions. II. Streptococcus faecalis. 679 2

A protein-protein association regulated by phosphorylation of tyrosine is examined by NMR structural studies and biochemical studies. Binding of glyceraldehyde-3-phosphate dehydrogenase (G3PDH) and aldolase to the N-terminus of human erythrocyte anion transporter, band 3, inhibits enzyme activity. This inhibition is reversed upon phosphorylation of band 3 Y8, as shown by kinetic studies on purified components, as well as in vivo studies. Thus, tyrosine phosphorylation mediates against the intermolecular protein-protein association, in contrast to the positive control involving SH2 and PTB domains where phosphorylation is required for binding. To elucidate the basis of recognition and negative control by tyrosine phosphorylation, the structure of a synthetic peptide, B3P, corresponding to the first 15 residues of band 3 (MEELQDDYEDMMEEN-NH2), bound to G3PDH has been determined using the exchange-transferred nuclear Overhauser effect. The G3PDH-bound B3P structure was found to be very similar to the structure recognized by aldolase. A hydrophobic triad forms from side chains within a loop structure of residues 4 through 9 in both bound species. Another structural feature stabilizing the loop, in the case of the B3P-G3PDH complex, is a hydrogen bond between the side chains of Y8 and D10 associated with a beta-turn of residues 8-11. Based on the structure of this phosphorylation sensitive interaction (PSI) loop, it is suggested that tyrosine phosphorylation disrupts protein-protein association, in part, by intramolecular electrostatic destabilization. The inhibition by B3P is competitive with respect to the coenzyme NAD+ and noncompetitive with the substrate analog arsenate. Specific binding of B3P to G3PDH is demonstrated by reversion of the NMR spectral properties of bound B3P to those of the free peptide upon addition of coenzyme and substrate analog. The stoichiometry of binding for the B3P-G3PDH complex was determined from Sephadex G-50 displacement experiments to be 4:1. Collectively, these results are consistent with B3P binding the active site of G3PDH.
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PMID:Insights into tyrosine phosphorylation control of protein-protein association from the NMR structure of a band 3 peptide inhibitor bound to glyceraldehyde-3-phosphate dehydrogenase. 945 76