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High-resolution X-ray structures of the complexes of Aspergillus flavus urate oxidase (Uox) with three inhibitors, 8-azaxanthin (AZA), 9-methyl uric acid (MUA) and oxonic acid (OXC), were determined in an orthorhombic space group (I222). In addition, the ligand-free enzyme was also crystallized in a monoclinic form (P2(1)) and its structure determined.(More)
Quantum chemical calculations are reported to provide new insights on plausible mechanisms leading to the deamidation of asparagine residues in proteins and peptides. Direct hydrolysis to aspartic acid and several succinimide-mediated mechanisms have been described. The catalytic effect of water molecules has been explicitly analyzed. Calculations have been(More)
This work examines the ability of semiempirical methods to describe the structure of liquid water. Particularly, the standard AM1 and PM3 methods together with recently developed PM3-PIF and PM3-MAIS parametrizations have been considered. We perform molecular dynamics simulations for a system consisting of 64 or 216 water molecules in a periodic cubic box.(More)
Deamidation of proteins occurs spontaneously under physiological conditions. Asparaginyl (Asn) residues may deamidate into aspartyl (Asp) residues, causing a change in both the charge and the conformation of peptides. It has been previously proposed by Capasso et al. that deamidation of relatively unrestrained Asn residues proceeds through a succinimide(More)
In a first step toward the development of an efficient and accurate protocol to estimate amino acids' pKa's in proteins, we present in this work how to reproduce the pKa's of alcohol and thiol based residues (namely tyrosine, serine, and cysteine) in aqueous solution from the knowledge of the experimental pKa's of phenols, alcohols, and thiols. Our protocol(More)
Urate oxidase (EC 1.7.3.3 or UOX) catalyzes the conversion of uric acid using gaseous molecular oxygen to 5-hydroxyisourate and hydrogen peroxide in absence of any cofactor or transition metal. The catalytic mechanism was investigated using X-ray diffraction, electron spin resonance spectroscopy (ESR), and quantum mechanics calculations. The X-ray structure(More)
Peptide-cyclodextrin and protein-cyclodextrin host-guest complexes are becoming more and more important for industrial applications, in particular in the fields of pharmaceutical and food chemistry. They have already deserved many experimental investigations although the effect of complex formation in terms of peptide (or protein) structure is not(More)
Urate oxidase catalyzes the transformation of uric acid in 5-hydroxyisourate, an unstable compound which is latter decomposed into allantoïn. Crystallographic data have shown that urate oxidase binds a dianion urate species deprotonated in N3 and N7, while kinetics experiments have highlighted the existence of several intermediates during catalysis. We have(More)
Deamidation of asparagine is the spontaneous degradation of this residue into aspartic acid. The kinetics of this slow reaction is mainly dependent on the nature of the adjacent amino acid that follows asparagine in a peptide or protein primary sequence. In the homodimer triosephosphate isomerase (TPI), there are two main deamidation sites per subunit:(More)
The localization of dioxygen sites in oxygen-binding proteins is a nontrivial experimental task and is often suggested through indirect methods such as using xenon or halide anions as oxygen probes. In this study, a straightforward method based on x-ray crystallography under high pressure of pure oxygen has been developed. An application is given on urate(More)