Exploring the pyridoxal 5′‐phosphate‐dependent enzymes

Abstract

Pyridoxal 5'-phosphate (PLP)-dependent enzymes represent about 4% of the enzymes classified by the Enzyme Commission. The versatility of PLP in carrying out a large variety of reactions exploiting the electron sink effect of the pyridine ring, the conformational changes accompanying the chemical steps and stabilizing distinct catalytic intermediates, and the spectral properties of the different coenzyme-substrate derivatives signaling the reaction progress, are some of the features that have attracted our interest to investigate the structure-dynamics-function relationships of PLP-dependent enzymes. To this goal, an integrated approach combining biochemical, biophysical, computational, and molecular biology methods was used. The extensive work carried out on two enzymes, tryptophan synthase and O-acetylserine sulfhydrylase, is presented and discussed as representative of other PLP-dependent enzymes we have investigated. Finally, perspectives of PLP-dependent enzymes functional genomics and drug targeting highlight the continuous novelty of an "old" class of enzymes.

Crystal Structure of Escherichia coli Diaminopropionate Ammonia-lyase Reveals Mechanism of Enzyme Activation and Catalysis

“…6C). The small peak observed at 340 nm may correspond to enolimine tautomer of PLP (47). The peak at 422 nm was higher than the peak at 412 nm in contrast to that of the wild type enzyme spectrum.…”

“…With increase in time, this peak reverted back to 412 nm with concomitant increase in the absorbance at 317 nm (because of the product pyruvate). Addition of D-DAP to D120N also resulted in a shift of absorbance maximum from 412 to 422 nm, indicating the formation of ketoenamine form of PLP external aldimine (47). However, no further changes in the spectrum were observed with change in time (Fig.…”

Defining the structural requirements for ribose 5‐phosphate‐binding and intersubunit cross‐talk of the malarial pyridoxal 5‐phosphate synthase

“…The C-terminal region from residue 273 on is in close proximity to helix a8 0 and the loop between b6 and a6 of the (ba) 8 -barrel (Fig. 1A) both of which have been implied in phosphate binding of the substrate R5P [10].…”

“…The metabolically active forms are pyridoxal 5-phosphate (PLP) und pyridoxamine 5-phosphate (PMP). PLP has been described as nature's most versatile cofactor and is involved in more than 100 enzymatic reactions [7,8]. In the malaria parasite, PLP is synthesized through the so-called deoxyxylose 5-phosphate independent pathway, in which the proteins Pdx1 and Pdx2 form a heteromeric class I glutamine amidotransferase [5,6].…”

Impact of disease-Linked mutations targeting the oligomerization interfaces of aldehyde dehydrogenase 7A1

“…1B) [3]. Given that roughly 4% of all enzymes employ PLP as a cofactor [6], reduced PLP levels could have a variety of adverse physiological consequences. Increased incidence of seizures is believed to be one of these [3].…”