RESUMO
The resistance of some penicillins to beta-lactamase enzymes was previously attributed to the nature of their C(6) side chain. In order to find explicitly the influence of the conformation of this side chain in the enzymatic mechanism, we have analyzed by experimental and theoretical methods (X-ray diffraction, NMR, IR, PCILO) the molecular structure of six resistant penicillins and derivatives: oxacillin, cloxacillin, dicloxacillin, flucloxacillin, methicillin, nafcillin, cloxacillin sulfoxide, and oxacillinpenicilloic acid. X-ray crystallography of flucloxacillin and nafcillin is fully described. We observe that the side chains of these penicillins have no influence on the electronic properties of the penam nucleus but are much more rigid than in the sensitive ones. The molecular conformations are mostly governed by the nonbonded Van der Waals interactions and, in the oxacillins, partly by the conjugation between exocyclic groups. The lack of flexibility could result in a distorting effect on the structure of the active site of the beta-lactamase, leading to the deactivation of the enzyme.
Assuntos
Penicilinase/metabolismo , Penicilinas , beta-Lactamases/metabolismo , Fenômenos Químicos , Química , Espectroscopia de Ressonância Magnética , Conformação Molecular , Penicilinas/metabolismo , Espectrofotometria Infravermelho , Difração de Raios XRESUMO
A combination of experimental and theoretical methods were used to investigate the stereoelectronic structure of zetidoline, a dopamine D2 receptor antagonist showing Na+-dependent binding. The solid-state conformation of zetidoline is characterized by synplanarity (coplanarity of the two rings with the chloro substituent and the carbonyl group on the same side). The side chain in the crystal adopts a folded conformation which places the azetidine nitrogen atom at about 8 A from the center of the aromatic ring. Quantum mechanical calculations indicate the synperiplanar and antiperiplanar conformations of the ring system to be of approximately equal energies. The molecular electrostatic potential of zetidoline in a nearly extended conformation shows a remarkable similarity with that of orthopramides (e.g. metoclopramide) and indolones (e.g. piquindone), i.e. two groups of drugs displaying the same D2 selectivity and Na+-dependent binding. We postulate that the close stereoelectronic similarity between zetidoline, orthopramides, and indolones accounts for their identical mechanism of action in the molecular level.
Assuntos
Imidazóis , Fenômenos Químicos , Físico-Química , Modelos Moleculares , Conformação Molecular , Receptores Dopaminérgicos/efeitos dos fármacos , Receptores de Dopamina D2 , Relação Estrutura-Atividade , Difração de Raios XRESUMO
The synthesis of six close analogues of baclofen [3-(4-chlorophenyl)-4-aminobutyric acid] (BAC), a potent GABAB agonist, are reported. The compounds were designed starting from the structural informations contained in the solid state of BAC, regarded as a possible bioactive conformation, in which the p-chlorophenyl ring is perpendicular to the GABA backbone. A similar conformational situation was created by rigidifying the BAC structure by means of methylene (1), ethylene (2 and 6), or propylene (3) units, or by introducing chlorine atoms (4 and 5) into the ortho positions ("ortho effect"). Only compound 5 showed affinity for the GABAB receptor. Compound 6 [1-(aminomethyl)-5-chloro-2,3-dihydro-1H-indene-1-acetic acid], which was initially considered as representing the optimal mimic of the solid-state conformation of BAC, was surprisingly found inactive. An extensive conformational analysis was performed on compounds 1-6 in order to evaluate their flexibility and the overlap of their conformational population with respect to BAC. For this purpose a distance map was generated from three possible pharmacophoric groups: the amino and the carboxylic functions, and the phenyl ring. Finally, several explanations are proposed to account for the poor affinities of the prepared compounds such as steric hindrance or flexibility demand of the receptor.
Assuntos
Baclofeno/análogos & derivados , Baclofeno/síntese química , Receptores de GABA-A/metabolismo , Animais , Baclofeno/química , Baclofeno/farmacologia , Ligação Competitiva , Membrana Celular/metabolismo , Indicadores e Reagentes , Modelos Moleculares , Conformação Molecular , Estrutura Molecular , Receptores de GABA-A/efeitos dos fármacos , Relação Estrutura-Atividade , Difração de Raios X , Ácido gama-Aminobutírico/química , Ácido gama-Aminobutírico/metabolismoRESUMO
The recently described potent and selective GABAA antagonist SR 95531 (gabazine) is compared to six other GABAA antagonists: (+)-bicuculline, (-)-securinine, (+)-tubocurarine, iso-THAZ, R-5135, and pitrazepine. Starting from ab initio molecular orbital calculations performed on crystal atomic coordinates, attempts were made to identify in each structure the functional groups that are involved in receptor recognition and binding. A molecular modeling study revealed that (a) all compounds possess accessible cationic and anionic sites separated by an 4.6-5.2 A intercharge distance, (b) the antagonistic nature of the compounds can be explained by the presence of additional binding sites, (c) the correct spatial orientation of the additional binding sites is crucial for GABAA selectivity, and (d) the criteria determining the potency of the antagonist effect are an accurate intercharge distance (greater than 5 A) and the existence of hydrogen-bonding functionalities on one of the additional ring system. The presented pharmacophore accounts also for the inactivity of closely related compounds such as (-)-bicuculline, adlumidine, virosecurinine, allosecurinine, and the 4,6-diphenyl analogue of gabazine.
Assuntos
Azepinas , Antagonistas de Receptores de GABA-A , Lactonas , Modelos Moleculares , Piperidinas , Alcaloides/química , Alcaloides/metabolismo , Alcaloides/farmacologia , Androstanos/química , Androstanos/metabolismo , Androstanos/farmacologia , Azasteroides/química , Azasteroides/metabolismo , Azasteroides/farmacologia , Bicuculina/química , Bicuculina/metabolismo , Bicuculina/farmacologia , Cristalização , Dibenzazepinas/química , Dibenzazepinas/metabolismo , Dibenzazepinas/farmacologia , Compostos Heterocíclicos de 4 ou mais Anéis , Compostos Heterocíclicos de Anel em Ponte , Isoxazóis/química , Isoxazóis/metabolismo , Isoxazóis/farmacologia , Conformação Molecular , Estrutura Molecular , Piridazinas/química , Piridazinas/metabolismo , Piridazinas/farmacologia , Receptores de GABA-A/metabolismo , Relação Estrutura-Atividade , Tubocurarina/química , Tubocurarina/metabolismo , Tubocurarina/farmacologia , Difração de Raios X , Ácido gama-Aminobutírico/químicaRESUMO
The crystal structures of 5-(5-furan-2-yl)-2'-deoxyuridine (II), 5-(5-bromofuran-2-yl)-2'-deoxyuridine (IV) and 5-(3-bromothien-2-yl)-2'-deoxyuridine (V) have been studied in order to explain the different affinity of the compounds for the herpes simplex virus type 1 (HSV-1) thymidine kinase. These compounds present a variable affinity according to the position of the heteroatom substituting the five-membered ring. An unfavourable substitution in the five-membered ring for interaction with the HSV-1 thymidine kinase has been identified.
Assuntos
Antivirais/química , Antivirais/metabolismo , Bromo , Desoxiuridina/química , Desoxiuridina/metabolismo , Herpesvirus Humano 1/enzimologia , Timidina Quinase/metabolismo , Desoxiuridina/análogos & derivados , Humanos , Relação Estrutura-Atividade , Tiofenos/química , Tiofenos/metabolismo , Difração de Raios XRESUMO
Structural and electronic characteristics of 5-(5-chlorothien-2-yl)-2'-deoxyuridine (I), 5-(furan-2-yl)-2'-deoxyuridine (II), 5-(5-bromofuran-2-yl)-2'-deoxyuridine (III), 5-(3-bromoisoxazol-5-yl)-2'-deoxyuridine (V) and 5-(isoxazol-5-yl)-2'-deoxyuridine (IV) have been determined and compared to the BVDU (VI) characteristics in order to explain their respective affinity for the herpes simplex virus type 1 thymidine kinase (TK). Molecular structure of 5-(5-chlorothien-2-yl)-2'-deoxyuridine has been obtained using single crystal X-ray crystallography. Electrostatic potential maps, energy and topology of frontier orbitals were computed at the ab initio MO STO-3G and STO-3G level. These studies reveal that the electrostatic potential energy maps are clearly dependent on the affinity of the compound for the enzyme.
Assuntos
Antivirais/química , Antivirais/farmacologia , Bromodesoxiuridina/análogos & derivados , Desoxiuridina/análogos & derivados , Desoxiuridina/farmacologia , Herpesvirus Humano 1/efeitos dos fármacos , Bromodesoxiuridina/química , Bromodesoxiuridina/farmacologia , Fenômenos Químicos , Físico-Química , Desoxiuridina/química , Estrutura Molecular , Estereoisomerismo , Termodinâmica , Tiofenos/química , Tiofenos/farmacologia , Timidina Quinase/química , Timidina Quinase/efeitos dos fármacos , Proteínas Virais/química , Proteínas Virais/efeitos dos fármacos , Difração de Raios XRESUMO
Experimental and theoretical physico-chemical methods were used to investigate the interaction between aryl-oxazolidinones and monoamine oxidase (MAO). Several arguments suggest that these compounds interact with the flavin adenine dinucleotide (FAD) cofactor of MAO. The calculation using ab initio molecular orbital methods of the electronic properties of flavin and befloxatone, a reversible inhibitor of MAO A, led to a description of the interaction between aryl-oxazolidinones and the cofactor of the enzyme. Structure activity relationship results revealed additional sites of interaction with the protein core of MAO A. As a result of this work, a model is proposed for the reversible inhibition of MAO by oxazolidinones via long distance, reversible interactions with the FAD cofactor of the enzyme.
Assuntos
Modelos Químicos , Inibidores da Monoaminoxidase/química , Inibidores da Monoaminoxidase/farmacologia , Fenômenos Químicos , Físico-Química , Oxazóis/química , Oxazóis/farmacologia , Relação Estrutura-Atividade , Difração de Raios XRESUMO
Hypoxia-inducible factor-1 (HIF-1) is a heterodimeric transcription factor activated by hypoxia. When activated, HIF-1 mediates the differential expression of genes such as erythropoietin and Vascular Endothelial Growth Factor (VEGF) during hypoxia. It is composed of two different subunits, HIF-1alpha and ARNT (Aryl Receptor Nuclear Translocator). These two subunits belong to the bHLH (basic Helix-Loop-Helix) PAS (Per, Ahr/ARNT, Sim) family. The bHLH domain of these factors is responsible for dimerization through the two helices and for DNA binding through their basic domain. In this work, we used various methods of molecular modeling in order to develop a 3D structure for the HIF-1 bHLH domain bound to its DNA consensus sequence. Firstly, the 3D structure of the bHLH domain of both subunits based on their amino acid sequence was defined. Secondly, we compared this model with data from known crystal structures of basic leucine zipper-DNA and bHLH-DNA complexes in order to determine a potential canvas for HIF-1. Thirdly, we performed a manual approach of the HIF-1 bHLH domain onto the DNA recognition site using this canvas. Finally, the protein-DNA complex 3D structure was optimized using a Monte Carlo program called MONTY. The model predicted a pattern of interactions between amino acids and DNA bases which reflect for ARNT what is experimentally observed among different X-ray structures of other bHLH transcription factors possessing the H (His), E (Glu), R (Arg) triad, as ARNT does. On the other hand, only the Arg residue is conserved in HIF- 1alpha. We propose from this model that a serine replaces the histidine while an alanine and a lysine also make contacts with DNA. From these results, we postulate that the specificity of HIF-1 toward its DNA sequence could be driven by the HIF-1alpha subunit. The predicted model will be verified by X-Ray currently ongoing.
Assuntos
Proteínas de Ligação a DNA/química , Proteínas Nucleares/química , Alanina/química , Sequência de Aminoácidos , Animais , Cristalografia , Dimerização , Eritropoetina/química , Histidina/química , Fator 1 Induzível por Hipóxia , Subunidade alfa do Fator 1 Induzível por Hipóxia , Lisina/química , Modelos Moleculares , Dados de Sequência Molecular , Método de Monte Carlo , Ligação Proteica , Conformação Proteica , Estrutura Secundária de Proteína , Estrutura Terciária de Proteína , Análise de Sequência de DNA , Serina/química , Software , Fatores de Transcrição/químicaRESUMO
Previous investigations of the potential of metal-organic compounds as inhibitors of human immunodeficiency virus type I protease (HIV-1 PR) showed that the copper(II) complex diaqua [bis(2-pyridylcarbonyl)amido] copper(II) nitrate dihydrate and the complex bis[N2-(2,3,6-trimethoxybenzyl)-4-2-pyridinecarboxamide] copper(II) behaved as inhibitors of HIV-1 PR. In a search for similar readily accessible ligands, we synthesised and studied the structural properties of N2-(2-pyridylmethyl)-2-pyridinecarboxamide (L) copper(II) complexes. Three different crystal structures were obtained. Two were found to contain ligand L simultaneously in a tridentate and bidentate conformation [Cu(L(tri)L(bi))]. The other contained two symmetry-related ligands, coordinated through the pyridine nitrogen and the amide oxygen atoms [Cu(L(bi))(2)]. A search of the Cambridge Structural Database indicated that L(tri) resulting from nitrogen bound amide hydrogen metal substitution is favoured over chelation through the amide oxygen atom. In our case, we calculated that the conformation of L(tri) is 11 kcal/mol more favourable than that of L(bi). ESI-MS experiments showed that the Cu(L(bi))(2) structure could not be observed in solution, while Cu(L(tri)L(bi))-related complexes were indeed present. The lack of protease inhibition of the pyridine carboxamide copper(II) complexes was explained by the fact that the Cu(L(bi)L(tri)) complex could not fit into the HIV-1 active site.
Assuntos
Cobre/química , Inibidores da Protease de HIV/química , Inibidores da Protease de HIV/síntese química , Compostos Organometálicos/química , Compostos Organometálicos/síntese química , Piridinas/química , Piridinas/síntese química , Domínio Catalítico , Cristalografia por Raios X , Desenho de Fármacos , Protease de HIV/química , Inibidores da Protease de HIV/farmacologia , Técnicas In Vitro , Modelos Moleculares , Compostos Organometálicos/farmacologia , Piridinas/farmacologia , Espectrometria de Massas por Ionização por ElectrosprayRESUMO
The structures, electronic (charges, molecular electrostatic potential, molecular orbitals) and lipophilic properties of three isostere analogues of torasemide were determined and the influence of the replacement of the sulfonyl urea group on the conformation and electronic properties of the molecules is discussed. Lipophilicity of the compounds seems to be the most discriminating property along the series and affects their pharmacological activities.
Assuntos
Diuréticos/química , Sulfonamidas/química , Animais , Cristalografia , Diuréticos/farmacologia , Isomerismo , Conformação Molecular , Relação Quantitativa Estrutura-Atividade , Ratos , Sulfonamidas/farmacologia , TorasemidaRESUMO
This work reports on the structure of trielaidin [EEE, 1,2,3-tri(trans-9-octadecenoyl)glycerol], a trans unsaturated triglyceride present in many refined fatty materials (margarines, chocolate products etc.). Firstly, the polymorphism, i.e. the existence of different crystalline forms at various temperature ranges, was defined. Secondly, the crystal growth was examined. By developing a particular growing system, monocrystals of the most stable polymorphic form, i.e. the beta-form, were obtained. To reduce thermal vibrations the X-ray data were collected at low temperature (173 K) and the structure was solved using direct methods. The structure was then analyzed in terms of conformation and crystal packing and compared with those of the other known triglycerides.
RESUMO
The synthesis and the structure of N-isopropyl-N'-[2-(3'-methylphenylamino)-5-nitrobenzenesulfonyl] urea (14) was drawn from two thromboxane A2 receptor antagonists structurally related to torasemide. Compound 14 showed an IC50 value of 22 nM for the thromboxane A2 (TXA2) receptor of human washed platelets. Compound 14 prevented platelet aggregation induced by arachidonic acid (0.6 mM) and U-46619 (1 microM) with an IC50 value of 0.45 and 0.15 microM, respectively. Moreover, 14 relaxed the rat isolated aorta and guinea-pig trachea precontracted by U-46619, a TXA2 agonist. Its efficacy (IC50) was 20.4 and 5.47 nM, respectively. Finally, 14 (1 microM) completely inhibited TXA2 synthase of human platelets. The pKa value and the crystallographic data of 14 were determined and used to propose an interaction model between the TXA2 antagonists related to torasemide and their receptor.
Assuntos
Receptores de Tromboxanos/antagonistas & inibidores , Compostos de Sulfonilureia/síntese química , Compostos de Sulfonilureia/farmacologia , Tromboxano-A Sintase/antagonistas & inibidores , Animais , Aorta/efeitos dos fármacos , Aorta/fisiologia , Ácido Araquidônico/farmacologia , Cobaias , Masculino , Agregação Plaquetária/efeitos dos fármacos , Ratos , Ratos Wistar , Tromboxano-A Sintase/metabolismo , Traqueia/efeitos dos fármacos , Traqueia/fisiologiaRESUMO
Crystallographic database studies and molecular dynamics simulations in different media have enabled us to sample the conformational space of a GABAB antagonist. As a result, we have defined a pharmacophoric pattern for GABAB antagonists. This study has led us to compare the conformational preferences deduced from database studies and molecular dynamics simulations. The influence of the medium on the conformations has also been investigated.
Assuntos
Antagonistas GABAérgicos/química , Antagonistas de Receptores de GABA-B , Modelos Moleculares , Baclofeno/análogos & derivados , Baclofeno/química , Simulação por Computador , Cristalografia , Bases de Dados Factuais , Agonistas GABAérgicos/química , Conformação Molecular , TermodinâmicaRESUMO
The crystal structure of seratrodast (AA-2414), a potent thromboxane A2 (TXA2) receptor antagonist, served as starting point to docking studies with the modeled human TXA2 receptor. This structural approach provides rational basis for the design of new antagonists within the aryl sulfonamide family.
Assuntos
Benzoquinonas/química , Ácidos Heptanoicos/química , Antagonistas de Prostaglandina/química , Receptores de Tromboxanos/química , Animais , Benzoquinonas/farmacologia , Cristalografia por Raios X , Desenho de Fármacos , Cobaias , Ácidos Heptanoicos/farmacologia , Modelos Moleculares , Conformação Molecular , Estrutura Molecular , Antagonistas de Prostaglandina/farmacologia , Receptores de Tromboxanos/antagonistas & inibidores , Sulfonamidas/química , Sulfonamidas/farmacologiaRESUMO
The major goal of the present work is to further approach the structure of human monoamine oxidase A (MAO-A). A first partial three-dimensional model of human MAO-A has already been established using secondary structure predictions and fold recognition methods [Wouters and Baudoux, 1998]. In this modeled structure, a segment of the sequence (residues 369-393) located near the covalent linkage to the essential flavin cofactor, and potentially involved in the structure of the active site of the protein, could not be modeled. We here propose a possible fold for that segment, based on threading techniques. The identification of regions of the protein potentially involved in its dimerization was also undertaken by studying hydrophobic areas present at the surface of the structure.
Assuntos
Modelos Moleculares , Monoaminoxidase/química , Humanos , Conformação ProteicaRESUMO
The presence and configuration (syn or anti) of an oxyimino group in the 7 (beta)-acyl side chain of 3-cephems do not modify the intrinsic reactivity of the beta-lactam ring, but have highly enzyme-specific effects. When compared with the corresponding desoxyimino beta-lactam compound: (i) with the plasmid-mediated Escherichia coli RTEM-2 serine beta-lactamase, the substrate activity of the anti isomer is increased and that of the syn isomer is decreased; (ii) with the Streptomyces R61 serine D-alanyl-D-alanine cleaving peptidase (a highly penicillin-sensitive enzyme), the rate of enzyme acylation is not or only little affected when the oxyimino group is in the syn configuration, but is decreased when the oxyimino group is in the anti configuration; (iii) with the Actinomadura R39 serine D-alanyl-D-alanine-cleaving peptidase (an exceedingly highly penicillin-sensitive enzyme), the rate of enzyme acylation is unaffected whatever the configuration of the substituent. The oxidation of the sulphur atom of the dihydrothiazine ring on the beta-face of the molecule makes it both a poorer inactivator of the DD-peptidases and a poorer substrate of the beta-lactamase. The Streptomyces albus G Zn2+-containing D-alanyl-D-alanine-cleaving peptidase (a highly penicillin-resistant enzyme) remains highly resistant to all compounds tested.
Assuntos
Cefalosporinas , Penicilinase , D-Ala-D-Ala Carboxipeptidase Tipo Serina , Carboxipeptidases/antagonistas & inibidores , Fenômenos Químicos , Química , Hidrólise , Cinética , Relação Estrutura-Atividade , Especificidade por SubstratoRESUMO
Molecular graphic design coupled with PCILO and crystallographic results have been used to investigate the three-dimensional structure of Tropapride, Piquindone, Zetidoline, and Metoclopramide, four dopamine D-2 receptor antagonists showing Na+-dependent binding. Three putative pharmacophoric elements, a nitrogen lone pair, a phenyl ring and a carbonyl moiety, are similarly oriented in all the Na+-dependent drugs. Conversely, for Na+-independent analogs, the two latter pharmacophoric elements play a subordinate role, but two pi-electron regions are systematically localized on the other side of the molecule: the first is a phenyl group while the second is a carbonyl function as in butyrophenones, a cyano group as in R48455, or a phenyl ring as in diphenylbutylpiperidines or tricyclics. The presence of a benzyl ring on this side in Tropapride might explain its weak extrapyramidal effects.
Assuntos
Antagonistas de Dopamina , Imidazóis , Isoquinolinas , Metoclopramida , Nortropanos , Sódio , Gráficos por Computador , Modelos Moleculares , Movimento (Física) , Receptores Dopaminérgicos/ultraestrutura , Relação Estrutura-AtividadeRESUMO
The crystal structures of three angiotensin-II receptor antagonists involving different spacer groups (CO, CONH and NHCO) between the aryl rings are presented, namely 2-[4-[(3-butyl-1,4-dioxo-2,3-diazaspiro[4.4]non-2-yl)methyl]benzoyl]benzoic acid, C(26)H(28)N(2)O(5), (I), 2-[4-[(3-butyl-1,4-dioxo-2,3-diazaspiro[4.4]non-2-yl)methyl]benzamido]benzoic acid, C(26)H(29)N(3)O(5), (II), and 2-[4-[(3-butyl-1,4-dioxo-2,3-diazaspiro[4.4]non-2-yl)methyl]anilinocarbonyl]benzoic acid monohydrate, C(26)H(29)N(3)O(5) x H(2)O, (III). The aryl rings of (II) are almost coplanar, in contrast with compounds (I) and (III). The conformation of (II) is induced by an intramolecular N-H.O hydrogen bond between the amide and carboxylic acid groups.
Assuntos
Angiotensina II , Antagonistas de Receptores de Angiotensina , Pirazóis/química , Cristalografia por Raios X , Ligação de Hidrogênio , Modelos Moleculares , Conformação MolecularRESUMO
The Hartree-Fock ab initio molecular orbital method has been applied to eight compounds: GABA (gamma-amino butyric acid) (1), its partially rigidified analog, TACA (trans-4-aminocrotonic acid) (2), six isoxazolol analogs; muscimol (5-aminomethylisoxazol-3-ol (3), THIP (4,5,6,7-tetrahydroisoxazolo[5,4-c]pyridin-3-ol) (4), THAZ (5,6,7,8-tetrahydro-4H-isoxazolo[4,5-d]azepin-3-ol) (5), isomuscimol (3-aminomethylisoxazol-5-ol) (6), iso-THIP (4,5,6,7-tetrahydroisoxazolo[3,4-c] pyridin-5-ol) (7), and iso-THAZ (5,6,7,8-tetrahydro-4H-isoxazolo[3,4-d]azepin-5-ol) (8). GABA is an endogenous inhibitory transmitter. The four following molecules (2), (3), (4) and (5) are agonist: they bind themselves to the GABA receptors and induce approximately the same effect as GABA. (6) is lightly agonist, presenting a lower affinity. Compounds (7) and (8) are antagonists, giving rise to convulsion. Optimized molecular conformations of GABA (1), muscimol (3) and isomuscimol (6) are discussed. Geometric and electronic parameters showing the presence of intramolecular hydrogen bonds are presented. The permutation of the heteroatoms in the isoxazole ring has no effect on the side-chain orientation explaining maybe the agonist character of isomuscimol, being able to adopt easily and exactly the active conformation. Atomic charge distributions and electronic overlap populations for all compounds have been computed in order to try to understand why their GABAergic activities can be so different. The computed values show that the 3-isoxazolol ring mimics in a good way the carboxylic function of GABA. They also illustrate the larger electronic delocalization within the 5-isoxazolol ring and therefore the resulting antagonist character, except for isomuscimol.
Assuntos
Antagonistas GABAérgicos , Fenômenos Químicos , Química , Crotonatos/farmacologia , Isoxazóis/farmacologia , Conformação Molecular , Muscimol/farmacologia , Piridinas/farmacologia , Receptores de GABA-A/metabolismoRESUMO
Amine oxidases (EC 1.4.3) represent a rather nebulous group of proteins with relative narrow substrate and inhibitor specificities. Several different enzymes fall into these amine oxidase classes and the classification of some of them still remains ambiguous. Kinetic and physico-chemical properties of tyramine oxidase of Arthrobacter sp. were investigated to decide if this enzyme belongs to the flavin containing tyramine oxidase class (EC 1.4.3.9) or if it is more related to another amine oxidase class. On the basis of its spectral characteristics, molecular weight and inhibition profile, the enzyme was identified as a semicarbazide sensitive copper-containing amine oxidase.