Book ChapterDOI
L-aspartase: new tricks from an old enzyme.
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TLDR
While the catalytic activity of this enzyme has been known for nearly 100 years, a number of recent studies have revealed some interesting and unexpected new properties of this reasonably well-characterized enzyme.Abstract:
The enzyme L-aspartate ammonia-lyase (aspartase) catalyzes the reversible deamination of the amino acid L-aspartic acid, using a carbanion mechanism to produce fumaric acid and ammonium ion. Aspartase is among the most specific enzymes known with extensive studies failing, until recently, to identify any alternative amino acid substrates that can replace L-aspartic acid. Aspartases from different organisms show high sequence homology, and this homology extends to functionally related enzymes such as the class II fumarases, the argininosuccinate and adenylosuccinate lyases. The high-resolution structure of aspartase reveals a monomer that is composed of three domains oriented in an elongated S-shape. The central domain, comprised of five-helices, provides the subunit contacts in the functionally active tetramer. The active sites are located in clefts between the subunits and structural and mutagenic studies have identified several of the active site functional groups. While the catalytic activity of this enzyme has been known for nearly 100 years, a number of recent studies have revealed some interesting and unexpected new properties of this reasonably well-characterized enzyme. The non-linear kinetics that are seen under certain conditions have been shown to be caused by the presence of a separate regulatory site. The substrate, aspartic acid, can also play the role of an activator, binding at this site along with a required divalent metal ion. Truncation of the carboxyl terminus of aspartase at specific positions leads to an enhancement of the catalytic activity of the enzyme. Truncations in this region also have been found to introduce a new, non-enzymatic biological activity into aspartase, the ability to specifically enhance the activation of plasminogen to plasmin by tissue plasminogen activator. Even after a century of investigation there are clearly a number of aspects of this multifaceted enzyme that remain to be explored.read more
Citations
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Journal ArticleDOI
High pressure enhancement of enzymes: A review
TL;DR: The compiled evidence of high pressure enzyme enhancement indicates that pressure is an effective reaction parameter with potential for greater utilization in enzyme catalysis.
Journal ArticleDOI
Amino acid-dependent growth of Campylobacter jejuni: key roles for aspartase (AspA) under microaerobic and oxygen-limited conditions and identification of AspB (Cj0762), essential for growth on glutamate
Edward Guccione,Maria del Rocio Leon-Kempis,Bruce M. Pearson,Edward Hitchin,Francis Mulholland,Pauline M. van Diemen,Mark P. Stevens,David J. Kelly +7 more
TL;DR: Stoichiometric aspartate uptake and succinate excretion involving the redundant DcuA and DcuB transporters indicated that in addition to a catabolic role, AspA can provide fumarate for respiration and suggest a role during growth in the avian gut.
Patent
Microorganisms for the production of adipic acid and other compounds
TL;DR: In this paper, a non-naturally occurring microbial organism having an adipate, 6-aminocaproic acid or caprolactam pathway was provided, where the microbial organism contained at least one exogenous nucleic acid encoding an enzyme in the respective pathway.
Journal ArticleDOI
Computational redesign of enzymes for regio- and enantioselective hydroamination.
Ruifeng Li,Hein J. Wijma,Lu Song,Yinglu Cui,Marleen Otzen,Yu’e Tian,Jiawei Du,Tao Li,Dingding Niu,Yanchun Chen,Jing Feng,Jian Han,Hao Chen,Yong Tao,Dick B. Janssen,Bian Wu +15 more
TL;DR: Computational protein design, without subsequent directed evolution, rapidly provides a set of aspartase variants capable of biocatalytic asymmetric addition of ammonia to substituted acrylates, producing various enantiopure β-amino acids.
Patent
Methods and organisms for utilizing synthesis gas or other gaseous carbon sources and methanol
TL;DR: In this article, a non-naturally occurring microbial organism having an acetyl-coenzyme A pathway and the capability of utilizing syngas and methanol was presented.
References
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Journal ArticleDOI
MOLSCRIPT: a program to produce both detailed and schematic plots of protein structures
TL;DR: The MOLSCRIPT program as discussed by the authors produces plots of protein structures using several different kinds of representations, including simple wire models, ball-and-stick models, CPK models and text labels.
Journal ArticleDOI
The cell biology of the plasminogen system.
TL;DR: Shared binding sites for lipoprotein(a) and plasmin(ogen) on cell surfaces and in the sub endothelial matrix may contribute to the pathogenetic risks associated with elevated levels of lipop protein(a).
Journal ArticleDOI
Artificial chaperones-protein refolding via sequential use of detergent and cyclodextrin
Journal ArticleDOI
Mutation of the fumarase gene in two siblings with progressive encephalopathy and fumarase deficiency.
Thomas Bourgeron,Dominique Chretien,J Poggi-Bach,S Doonan,D. Rabier,P Letouzé,Arnold Munnich,Agnès Rötig,P. Landrieu,Pierre Rustin +9 more
TL;DR: The present study is to the authors' knowledge the first molecular characterization of tricarboxylic acid deficiency, a rare inherited inborn error of metabolism in childhood.
Journal ArticleDOI
l-Phenylalanine ammonia-lyase: IV. Evidence that the prosthetic group contains a dehydroalanyl residue and mechanism of action
TL;DR: It is proposed that the active site contains a dehydroalanyl residue which upon reduction yields a tritiated alanyl residue so substituted at the nitrogen atom that HCl hydrolysis leads to racemization and tritium loss.