At last--the crystal structure of urease
19 May 1995-Science (American Association for the Advancement of Science)-Vol. 268, Iss: 5213, pp 996-997
About: This article is published in Science.The article was published on 1995-05-19. It has received 88 citations till now. The article focuses on the topics: Crystal structure.
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TL;DR: This review will summarize first the general structural features of organocopper compounds and the previous mechanistic arguments, and then describe the most recent mechanistic pictures obtained through high-level quantum mechanical calculations for three typical organocuprate reactions, carbocupration, conjugate addition, and S(N)2 alkylation.
Abstract: Organocopper reagents provide the most general synthetic tools in organic chemistry for nucleophilic delivery of hard carbanions to electrophilic carbon centers. A number of structural and mechanistic studies have been reported and have led to a wide variety of mechanistic proposals, some of which might even be contradictory to others. With the recent advent of physical and theoretical methodologies, the accumulated knowledge on organocopper chemistry is being put together into a few major mechanistic principles. This review will summarize first the general structural features of organocopper compounds and the previous mechanistic arguments, and then describe the most recent mechanistic pictures obtained through high-level quantum mechanical calculations for three typical organocuprate reactions, carbocupration, conjugate addition, and S(N)2 alkylation. The unified view on the nucleophilic reactivities of metal organocuprate clusters thus obtained has indicated that organocuprate chemistry represents an intricate example of molecular recognition and supramolecular chemistry, which chemists have long exploited without knowing it. Reasoning about the uniqueness of the copper atom among neighboring metal elements in the periodic table will be presented.
223 citations
TL;DR: Data indicate that labile, nonactivating complexes between the SE9 TCR and most HLA-DR/peptide conjugates might supply sterically optimized coordination sites for Ni ions, three of which were identified in this study.
Abstract: In spite of high frequencies of metal allergies, the structural basis for major histocompatibility complex (MHC)-restricted metal recognition is among the unanswered questions in the field of T cell activation. For the human T cell clone SE9, we have identified potential Ni contact sites in the T cell receptor (TCR) and the restricting human histocompatibility leukocyte antigen (HLA)-DR structure. The specificity of this HLA-DR-promiscuous VA22/VB17+ TCR is primarily harbored in its alpha chain. Ni reactivity is neither dependent on protein processing in antigen-presenting cells nor affected by the nature of HLA-DR-associated peptides. However, SE9 activation by Ni crucially depends on Tyr29 in CDR1alpha, an N-nucleotide-encoded Tyr94 in CDR3alpha, and a conserved His81 in the HLA-DR beta chain. These data indicate that labile, nonactivating complexes between the SE9 TCR and most HLA-DR/peptide conjugates might supply sterically optimized coordination sites for Ni ions, three of which were identified in this study. In such complexes Ni may effectively bridge the TCR alpha chain to His81 of most DR molecules. Thus, in analogy to superantigens, Ni may directly link TCR and MHC in a peptide-independent manner. However, unlike superantigens, Ni requires idiotypic, i.e., CDR3alpha-determined TCR amino acids. This new type of TCR-MHC linkage might explain the high frequency of Ni-reactive T cells in the human population.
138 citations
Cites background from "At last--the crystal structure of u..."
...Moreover, in the Ni complex of bacterial urease two of six Ni coordination sites are occupied by oxygens of water molecules (41, 42)....
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TL;DR: In this paper, a number of enzymatalyse of metallionen have been charakterisiert, in denen zwei oder mehrere benachbarte Metallionen die Katalyse von Phosphoryl- (ROPO3 + R′OH R′OPO 3 + ROH; im Fall der Phosphatasereaktion ist R′-OH ein Wassermolekul) and von Carbonyltransferreaktionen unterstutzen, z. B
Abstract: Sowohl bei enzymatischen als auch bei nichtenzymatischen Katalysen sind zahlreiche Untersuchungen durchgefuhrt worden, um zu verstehen, wie Metallionen – besonders Zinkionen – die Hydrolyse von Phosphorsaureester- und Amidbindungen unterstutzen. Hydrolasen mit einem Metallion im aktiven Zentrum, sogenannte mononucleare Metallohydrolasen, z. B. die Carboxypeptidase A oder Thermolysin, zahlen zu den ersten Enzymen, deren Strukturen rontgenographisch aufgeklart werden konnten. In den letzten Jahren wurden zunehmend mehr Metalloenzyme charakterisiert, in denen zwei oder mehrere benachbarte Metallionen die Katalyse von Phosphoryl- (ROPO3 + R′OH R′OPO3 + ROH; im Fall der Phosphatasereaktion ist R′-OH ein Wassermolekul) und von Carbonyltransferreaktionen unterstutzen, z. B. in Peptidasen und anderen Amidasen. Diese dinuclearen Metalloenzyme katalysieren enorm viele Reaktionen dieser Art: die hydrolytische Spaltung von Phosphorsauremono-, di- und triesterbindungen, von Phosphorsaureanhydridbindungen sowie die Spaltung von Peptidbindungen oder Harnstoff. Auch die Bildung der Phosphodiesterbindung in RNA und DNA wird von Polymerasen uber einen Zwei-Metallionen-Mechanismus katalysiert. Erstaunlich vielfaltig sind auch die Strukturen der aktiven Zentren dieser di- oder trinuclearen Metalloenzyme, selbst fur Enzyme, die sehr ahnliche Reaktionen katalysieren. Die Strukturbestimmung des aktiven und inaktivierten Enzyms mit gebundenem Substrat oder Produkt, einem stabilen Intermediat oder einem Analogon einer sich im Verlauf der Reaktion bildenden Zwischenstufe ist eine leistungsstarke Methode zur Aufklarung der mechanistischen Details der Enzymkatalyse. Strukturbestimmungen sind fur viele der in diesem Artikel beschriebenen Metalloenzyme durchgefuhrt worden und liefern zusammen mit anderen biochemischen Untersuchungen einen immer besseren Einblick in die Fragestellung, wie die zwei (oder mehr) Metallionen zusammenwirken, um die Reaktionen effizient zu katalysieren.
86 citations
TL;DR: The current review article summarizes and discusses endeavours towards the developments in the burgeoning field of urease inhibition in medicinal chemistry, with an emphasis on the insights that have been gleaned into the structural features that contribute to high and promising levels of anti‐urease activity.
Abstract: Ureases have emerged as significant virulence factors implicated in the pathogenesis of many clinical conditions such as pyelonephritis, hepatic coma, peptic ulceration, and the formation of injection-induced urinary stones and stomach cancer They have also been identified as important targets in research both for human and animal health, as well as in agriculture Strategies based on urease inhibition are the main treatment of diseases caused by urease-producing bacteria So, in the present context, a diverse library of chemical structures is known to possess remarkable inhibitory activities against urease enzymes The current review article summarizes and discusses endeavours towards the developments in the burgeoning field of urease inhibition in medicinal chemistry, with an emphasis on the insights that have been gleaned into the structural features that contribute to high and promising levels of anti-urease activity
71 citations
TL;DR: Two dinucleating pyrazole ligands HL1 and HL2 bearing 1,4-diisopropyl-1,4,7-triazacyclononane (iPr2TACN) side arms in the 3 and 5 positions have been synthesized by multi-step synthetic procedures as mentioned in this paper.
69 citations
References
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TL;DR: The mechanism postulates that chemical catalysis is facilitated by two divalent metal ions 3.9 A apart, as in phosphoryl transfer reactions catalyzed by protein enzymes, such as the 3',5'-exonuclease of Escherichia coli DNA polymerase I.
Abstract: A mechanism is proposed for the RNA-catalyzed reactions involved in RNA splicing and RNase P hydrolysis of precursor tRNA. The mechanism postulates that chemical catalysis is facilitated by two divalent metal ions 3.9 A apart, as in phosphoryl transfer reactions catalyzed by protein enzymes, such as the 3',5'-exonuclease of Escherichia coli DNA polymerase I. One metal ion activates the attacking water or sugar hydroxyl, while the other coordinates and stabilizes the oxyanion leaving group. Both ions act as Lewis acids and stabilize the expected pentacovalent transition state. The symmetry of a two-metal-ion catalytic site fits well with the known reaction pathway of group I self-splicing introns and can also be reconciled with emerging data on group II self-splicing introns, the spliceosome, and RNase P. The role of the RNA is to position the two catalytic metal ions and properly orient the substrates via three specific binding sites.
1,089 citations
TL;DR: A means of obtaining from the jack bean a new protein which crystallizes beautifully and whose solutions possess to an extraordinary degree the ability to decompose urea into ammonium carbonate is discovered.
767 citations
725 citations
340 citations
TL;DR: A mechanism of action for urease is proposed which involves initially an O-bonded complex between urea and an active-site Ni2+ ion and subsequently anO-bonding carbamato-enzyme intermediate.
Abstract: Acetamide and N-methylurea have been shown for the first time to be substrates for jack bean urease. In the enzymatic hydrolysis of urea, formamide, acetamide, and N-methylurea at pH 7.0 and 38 degrees C, kcat has the values 5870, 85, 0.55, and 0.075 s-1, respectively. The urease-catalyzed hydrolysis of all these substrates involves the active-site nickel ion(s). Enzymatic hydrolysis of the following compounds could not be detected: phenyl formate, p-nitroformanilide, trifluoroacetamide, p-nitrophenyl carbamate, thiourea, and O-methylisouronium ion. In the enzymatic hydrolysis of urea, the pH dependence of kcat between pH 3.4 and 7.8 indicates that at least two prototropic forms are active. Enzymatic hydrolysis of urea in the presence of methanol gave no detectable methyl carbamate. A mechanism of action for urease is proposed which involves initially an O-bonded complex between urea and an active-site Ni2+ ion and subsequently an O-bonded carbamato-enzyme intermediate.
190 citations