scholarly journals The disease-associated mutation of the mitochondrial thiol oxidase Erv1 impairs cofactor binding during its catalytic reaction

2014 ◽  
Vol 464 (3) ◽  
pp. 449-459 ◽  
Author(s):  
Efrain Ceh-Pavia ◽  
Swee Kim Ang ◽  
Michael P. Spiller ◽  
Hui Lu
Keyword(s):  
Catalytic Reaction ◽  
Molecular Basis ◽  
Cofactor Binding ◽  
Catalytic Intermediates ◽  
Functional Defect ◽  
Thiol Oxidase

Erv1 is a mitochondrial FAD-dependent thiol oxidase. We show that the Erv1 R182H mutant impairs cofactor binding to its catalytic intermediates, providing a model for molecular basis of the functional defect of the disease-associated mutation.

Molecular basis of the inhibitor selectivity and insights into the feedback inhibition mechanism of citramalate synthase from Leptospira interrogans

2009 ◽  
Vol 421 (1) ◽  
pp. 133-143 ◽  
Author(s):  
Peng Zhang ◽  
Jun Ma ◽  
Zilong Zhang ◽  
Manwu Zha ◽  
Hai Xu ◽  
...  
Keyword(s):  
Crystal Structure ◽  
Catalytic Reaction ◽  
Molecular Basis ◽  
High Selectivity ◽  
Feedback Inhibition ◽  
Biochemical Study ◽  
Inhibition Mechanism ◽  
Leptospira Interrogans ◽  
Regulatory Domain ◽  
Dimer Interface

LiCMS (Leptospira interrogans citramalate synthase) catalyses the first reaction of the isoleucine biosynthesis pathway in L. interrogans, the pathogen of leptospirosis. The catalytic reaction is regulated through feedback inhibition by its end product isoleucine. To understand the molecular basis of the high selectivity of the inhibitor and the mechanism of feedback inhibition, we determined the crystal structure of LiCMSC (C-terminal regulatory domain of LiCMS) in complex with isoleucine, and performed a biochemical study of the inhibition of LiCMS using mutagenesis and kinetic methods. LiCMSC forms a dimer of dimers in both the crystal structure and solution and the dimeric LiCMSC is the basic functional unit. LiCMSC consists of six β-strands forming two anti-parallel β-sheets and two α-helices and assumes a βαβ three-layer sandwich structure. The inhibitor isoleucine is bound in a pocket at the dimer interface and has both hydrophobic and hydrogen-bonding interactions with several conserved residues of both subunits. The high selectivity of LiCMS for isoleucine over leucine is primarily dictated by the residues, Tyr430, Leu451, Tyr454, Ile458 and Val468, that form a hydrophobic pocket to accommodate the side chain of the inhibitor. The binding of isoleucine has inhibitory effects on the binding of both the substrate, pyruvate, and coenzyme, acetyl-CoA, in a typical pattern of K-type inhibition. The structural and biochemical data from the present study together suggest that the binding of isoleucine affects the binding of the substrate and coenzyme at the active site, possibly via conformational change of the dimer interface of the regulatory domain, leading to inhibition of the catalytic reaction.

Prothrombin and β2-glycoprotein I frequently contribute to antiphospholipid antibody interactions with phospholipids and the generation of abnormal waveform profiles in coagulation assays

2003 ◽  
Vol 90 (08) ◽  
pp. 218-226 ◽  
Author(s):  
Zuowei Su ◽  
Tomonori Izumi ◽  
Thomas Ortel
Keyword(s):  
Prothrombin Time ◽  
Antiphospholipid Antibodies ◽  
Molecular Basis ◽  
Annexin V ◽  
Antiphospholipid Antibody ◽  
Cofactor Binding ◽  
Coagulation Assays ◽  
The Core ◽  
Glycoprotein I ◽  
Antibody Interactions

SummaryTransmittance waveforms are generated during clot formation on photo-optical coagulation analyzers. We previously showed that 61.5% of patients with antiphospholipid antibodies (APLA) exhibited a negative deflection in the pre-coagulation phase of the prothrombin time (PT slope 1). The current studies investigated the ‘molecular basis’ of this abnormal parameter. We found that the negative PT slope 1 is IgG-mediated and is not dependent on the presence of fibrinogen or thrombin activity. We also found that IgG from most of the patients required a specific thromboplastin and the presence of prothrombin or β2-glycoprotein I (β2GPI) to produce an abnormal IgG waveform assay. In addition, the abnormal IgG waveform required cofactor binding to phospholipids when β2GPI was the cofactor, and annexin V could partially block this interaction. In conclusion, these results showed that the interactions of IgG with phospholipids via β2GPI or prothrombin constitute the core mechanisms of the abnormal waveforms.

Renilla Bioluminescence: A Morphologic Approach to the Location of Photocytes

1974 ◽  
Vol 32 ◽  
pp. 208-209
Author(s):  
Ben O. Spurlock ◽  
Milton J. Cormier
Keyword(s):  
Excited State ◽  
Ground State ◽  
Molecular Basis ◽  
Light Emission ◽  
Chemical Basis ◽  
Electronic Excited State ◽  
Colonial Form ◽  
The Common ◽  
Eighteenth And Nineteenth Centuries ◽  
Catalyzed Oxidation

The phenomenon of bioluminescence has fascinated layman and scientist alike for many centuries. During the eighteenth and nineteenth centuries a number of observations were reported on the physiology of bioluminescence in Renilla, the common sea pansy. More recently biochemists have directed their attention to the molecular basis of luminosity in this colonial form. These studies have centered primarily on defining the chemical basis for bioluminescence and its control. It is now established that bioluminescence in Renilla arises due to the luciferase-catalyzed oxidation of luciferin. This results in the creation of a product (oxyluciferin) in an electronic excited state. The transition of oxyluciferin from its excited state to the ground state leads to light emission.

Androgen-induced plasticity at a “vocal” neuromuscular synapse

1994 ◽  
Vol 52 ◽  
pp. 32-33
Author(s):  
Darcy B. Kelley ◽  
Martha L. Tobias ◽  
Mark Ellisman
Keyword(s):  
Xenopus Laevis ◽  
Motor Neurons ◽  
Sexual Differentiation ◽  
Molecular Basis ◽  
Neuromuscular Synapse ◽  
Sexually Dimorphic ◽  
Intracellular Protein ◽  
Developmental Program ◽  
Androgen Action ◽  
Clawed Frog

Brain and muscle are sexually differentiated tissues in which masculinization is controlled by the secretion of androgens from the testes. Sensitivity to androgen is conferred by the expression of an intracellular protein, the androgen receptor. A central problem of sexual differentiation is thus to understand the cellular and molecular basis of androgen action. We do not understand how hormone occupancy of a receptor translates into an alteration in the developmental program of the target cell. Our studies on sexual differentiation of brain and muscle in Xenopus laevis are designed to explore the molecular basis of androgen induced sexual differentiation by examining how this hormone controls the masculinization of brain and muscle targets.Our approach to this problem has focused on a highly androgen sensitive, sexually dimorphic neuromuscular system: laryngeal muscles and motor neurons of the clawed frog, Xenopus laevis. We have been studying sex differences at a synapse, the laryngeal neuromuscular junction, which mediates sexually dimorphic vocal behavior in Xenopus laevis frogs.

A molecular basis for opiate action

1998 ◽  
Vol 33 ◽  
pp. 65-77 ◽  
Author(s):  
Dominique Massotte ◽  
Brigitte L. Kieffer
Keyword(s):  
Molecular Basis

Emerging Nutrition Gaps in a World of Affluence - Micronutrient Intake and Status Globally

2011 ◽  
Vol 81 (4) ◽  
pp. 238-239 ◽  
Author(s):  
Manfred Eggersdorfer ◽  
Paul Walter
Keyword(s):  
Developing Countries ◽  
Human Health ◽  
Old Age ◽  
Molecular Basis ◽  
Health Benefit ◽  
Developed Countries ◽  
Micronutrient Deficiencies ◽  
New Science ◽  
Health And Nutrition ◽  
Micronutrient Intake

Nutrition is important for human health in all stages of life - from conception to old age. Today we know much more about the molecular basis of nutrition. Most importantly, we have learnt that micronutrients, among other factors, interact with genes, and new science is increasingly providing more tools to clarify this interrelation between health and nutrition. Sufficient intake of vitamins is essential to achieve maximum health benefit. It is well established that in developing countries, millions of people still suffer from micronutrient deficiencies. However, it is far less recognized that we face micronutrient insufficiencies also in developed countries.

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