The high-resolution crystal structure of periplasmic Haemophilus influenzae NAD nucleotidase reveals a novel enzymatic function of human CD73 related to NAD metabolism

2011 ◽  
Vol 441 (1) ◽  
pp. 131-141 ◽  
Author(s):  
Silvia Garavaglia ◽  
Santina Bruzzone ◽  
Camilla Cassani ◽  
Laura Canella ◽  
Gianna Allegrone ◽  
...  
Keyword(s):  
Structural Analysis ◽  
Haemophilus Influenzae ◽  
Structural Investigation ◽  
Adenosine Monophosphate ◽  
Maximal Activity ◽  
Nad Metabolism ◽  
Nicotinamide Riboside ◽  
Enzymatic Function ◽  
Adenosine Phosphates ◽  
Periplasmic Enzyme

Haemophilus influenzae is a major pathogen of the respiratory tract in humans that has developed the capability to exploit host NAD(P) for its nicotinamide dinucleotide requirement. This strategy is organized around a periplasmic enzyme termed NadN (NAD nucleotidase), which plays a central role by degrading NAD into adenosine and NR (nicotinamide riboside), the latter being subsequently internalized by a specific permease. We performed a biochemical and structural investigation on H. influenzae NadN which determined that the enzyme is a Zn2+-dependent 5′-nucleotidase also endowed with NAD(P) pyrophosphatase activity. A 1.3 Å resolution structural analysis revealed a remarkable conformational change that occurs during catalysis between the open and closed forms of the enzyme. NadN showed a broad substrate specificity, recognizing either mono- or di-nucleotide nicotinamides and different adenosine phosphates with a maximal activity on 5′-adenosine monophosphate. Sequence and structural analysis of H. influenzae NadN led us to discover that human CD73 is capable of processing both NAD and NMN, therefore disclosing a possible novel function of human CD73 in systemic NAD metabolism. Our data may prove to be useful for inhibitor design and disclosed unanticipated fascinating evolutionary relationships.

scholarly journals Vaccine candidate P6 of nontypable Haemophilus influenzae is not a transmembrane protein based on protein structural analysis

Vaccine ◽  
2011 ◽  
Vol 29 (8) ◽  
pp. 1624-1627 ◽  
Author(s):  
Lea Vacca Michel ◽  
Breanna Kalmeta ◽  
Mark McCreary ◽  
Joy Snyder ◽  
Paul Craig ◽  
...  
Keyword(s):  
Structural Analysis ◽  
Haemophilus Influenzae ◽  
Vaccine Candidate ◽  
Transmembrane Protein ◽  
Protein Structural Analysis

scholarly journals PnuC and the Utilization of the Nicotinamide Riboside Analog 3-Aminopyridine in Haemophilus influenzae

2004 ◽  
Vol 48 (12) ◽  
pp. 4532-4541 ◽  
Author(s):  
Elizabeta Sauer ◽  
Melisa Merdanovic ◽  
Anne Price Mortimer ◽  
Gerhard Bringmann ◽  
Joachim Reidl
Keyword(s):  
Haemophilus Influenzae ◽  
Pasteurella Multocida ◽  
Growth Inhibitor ◽  
Narrow Host Range ◽  
Nicotinamide Riboside ◽  
E Coli ◽  
Nicotinamide Mononucleotide ◽  
The Family ◽  
Serovar Typhimurium ◽  
Utilization Pathway

ABSTRACT The utilization pathway for the uptake of NAD and nicotinamide riboside was previously characterized for Haemophilus influenzae. We now report on the cellular location, topology, and substrate specificity of PnuC. pnuC of H. influenzae is only distantly related to pnuC of Escherichia coli and Salmonella enterica serovar Typhimurium. When E. coli PnuC was expressed in an H. influenzae pnuC mutant, it was able to take up only nicotinamide riboside and not nicotinamide mononucleotide. Therefore, we postulated that PnuC transporters in general possess specificity for nicotinamide riboside. Earlier studies showed that 3-aminopyridine derivatives (e.g., 3-aminopyridine adenine dinucleotide) are inhibitory for H. influenzae growth. By testing characterized strains with mutations in the NAD utilization pathway, we show that 3-aminopyridine riboside is inhibitory to H. influenzae and is taken up by the NAD-processing and nicotinamide riboside route. 3-Aminopyridine riboside is utilized effectively in a pnuC+ background. In addition, we demonstrate that 3-aminopyridine adenine dinucleotide resynthesis is produced by NadR. 3-Aminopyridine riboside-resistant H. influenzae isolates were characterized, and mutations in nadR could be detected. We also tested other species of the family Pasteurellaceae, Pasteurella multocida and Actinobacillus actinomycetemcomitans, and found that 3-aminopyridine riboside does not act as a growth inhibitor; hence, 3-aminopyridine riboside represents an anti-infective agent with a very narrow host range.

Structural investigation of supported Cun clusters under vacuum and ambient air conditions using EXAFS spectroscopy

2016 ◽  
Vol 6 (18) ◽  
pp. 6942-6952 ◽  
Author(s):  
S. Peredkov ◽  
S. Peters ◽  
M. Al-Hada ◽  
A. Erko ◽  
M. Neeb ◽  
...  
Keyword(s):  
Fine Structure ◽  
Structural Analysis ◽  
Structural Investigation ◽  
Ambient Air ◽  
Exafs Spectroscopy ◽  
X Ray ◽  
Absorption Fine ◽  
X Ray Absorption

Structural analysis of deposited nanoclusters using extended X-ray absorption fine structure (EXAFS) spectroscopy.

scholarly journals Modelling and Structural Analysis of Three-Dimensional Wing

2019 ◽  
Vol 9 (1) ◽  
pp. 6820-6828
Keyword(s):  
Finite Element Analysis ◽  
Finite Element ◽  
Structural Analysis ◽  
Elastic Strain ◽  
Structural Investigation ◽  
Three Dimensional ◽  
Structural Behavior ◽  
Natural Rate ◽  
Modal Shape ◽  
Element Analysis

This paper attempts to discover the structural behavior of the wing imperiled to flowing loads through the voyage. The study uses a method in the form of finite element analysis of wing flexure distortion. As a first step, two wing models are established by captivating factual features, wing assembly, and plan principles into consideration. The gathering wing prototypical entails of tinny membrane, two poles, and multi-ribs. Two spars which consist of primary and secondary spars. NACA 23015 is chosen as the baseline aerofoil as this is identical alike to the tailored aerofoil being castoff in Airbus A320. Two rods mostly endure the twisting moment and trim strength, which is finished of titanium contaminant to ensure enough inflexibility. The covering and wing spars are made of aluminum amalgam to lessen the structural heaviness. Later, a static structural investigation is smeared, and the overall distortion, comparable elastic strain, and corresponding VonMises tension are obtained to analyze the mechanical behavior of the wing. Furthermore, modal investigation is being supported out to determine the natural rate of recurrence, as well as the modal shape of the three orders, which are acquired through the pre-stress modal analysis. The outcomes of the modal scrutiny aid engineers decrease excitation on the natural occurrences and avert the wing from the flurry. In view of the results obtained from the study, designers can emphasize consolidation and analysis the stress attentiveness range and huge distortion area. In conclusion, the recreation consequences indicate that the arrangement is possible and improves the information grade of the lifting surface.

scholarly journals Structural analysis of a novel substrate-free form of the aminoglycoside 6′-N-acetyltransferase from Enterococcus faecium

2020 ◽  
Vol 76 (8) ◽  
pp. 364-371
Author(s):  
Hyunseok Jang ◽  
Sunghark Kwon ◽  
Chang-Sook Jeong ◽  
Chang Woo Lee ◽  
Jisub Hwang ◽  
...  
Keyword(s):  
Crystal Structure ◽  
Structural Analysis ◽  
Mechanism Of Action ◽  
Enterococcus Faecium ◽  
Free Form ◽  
Amino Group ◽  
Detailed Mechanism ◽  
Conformational Selection ◽  
Enzymatic Function ◽  
Acetyl Group

Aminoglycoside acetyltransferases (AACs) catalyze the transfer of an acetyl group between acetyl-CoA and an aminoglycoside, producing CoA and an acetylated aminoglycoside. AAC(6′)-Ii enzymes target the amino group linked to the 6′ C atom in an aminoglycoside. Several structures of the AAC(6′)-Ii from Enterococcus faecium [Ef-AAC(6′)-Ii] have been reported to date. However, the detailed mechanism of its enzymatic function remains elusive. In this study, the crystal structure of Ef-AAC(6′)-Ii was determined in a novel substrate-free form. Based on structural analysis, it is proposed that Ef-AAC(6′)-Ii sequentially undergoes conformational selection and induced fit for substrate binding. These results therefore provide a novel viewpoint on the mechanism of action of Ef-AAC(6′)-Ii.

Synthesis, spectroscopic and structural analysis of a melamine copper complex

2014 ◽  
Vol 70 (a1) ◽  
pp. C1239-C1239
Author(s):  
Amani Direm ◽  
Noureddine Dadda ◽  
Wahiba Falek ◽  
Zina Boutobba ◽  
Nourredine Benali-Cherif
Keyword(s):  
Structural Analysis ◽  
Copper Complex ◽  
Structural Investigation ◽  
Three Dimensional ◽  
Building Blocks ◽  
The Other ◽  
X Ray Diffraction ◽  
X Ray ◽  
Supramolecular Architectures ◽  
Carboxylic Anions

Owing to its multiple sites acting as H-bonds' donors, melamine and its derivatives are considered as excellent building blocks for the construction of various crystalline supramolecular architectures based on phosphate, sulfate, chloride and carboxylic anions [1-10] on one hand and chlorometallate anions on the other hand [11-13]. In our contribution, we will discuss the synthesis, FTIR spectra and the structural investigation using the single crystal X-ray diffraction of (H2Melamine) [CuCl5]Cl, (I). The structural analysis of (I) revealed that it consists of alternating negative and positive layers running through the a-axis direction. The negative layers are built up of alternatively CuCl53- and discrete non-coordination Cl- anions, whereas the positive sheets are formed of [H2melamine2+]2 Hydrogen-bonded dimers. The N-H...N and N-H...Cl interactions are assembled to build three-dimensional H-bond patterns which insure the cohesion within the lattice (Fig. 01). A previous work showed that (I) exhibits antiferromagnetic properties [14]

Insufficient Maintenance an Achilles Heel of the Broumov Group of Churches

2015 ◽  
Vol 1122 ◽  
pp. 261-264 ◽  
Author(s):  
Giulia Facelli ◽  
Pavel Kuklik
Keyword(s):  
Structural Analysis ◽  
Cultural Heritage ◽  
Structural Investigation ◽  
Numerical Analyses ◽  
European Cooperation ◽  
Roof Structure ◽  
Current State ◽  
Young Students

As part of European cooperation here is presented collaboration among Universities on Structural Analysis of Historical Constructions, which gives the chance to international young students and professionals to take part on investigations of selected cultural heritage treasures. This report summarizes a structural investigation on two churches from the Broumov Group. The attention was focused on damages within the walls and the roof structure. Moreover laboratory and numerical analyses permitted to gather very important information on the current state of the two buildings and led to several remarks recommendations.

scholarly journals In Vitro Pharmacodynamic Activities of ABT-492, a Novel Quinolone, Compared to Those of Levofloxacin against Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis

2004 ◽  
Vol 48 (1) ◽  
pp. 203-208 ◽  
Author(s):  
Shana M. Gunderson ◽  
Robert A. Hayes ◽  
John P. Quinn ◽  
Larry H. Danziger
Keyword(s):  
Streptococcus Pneumoniae ◽  
Haemophilus Influenzae ◽  
Moraxella Catarrhalis ◽  
Maximal Activity ◽  
Community Acquired Pneumonia ◽  
Maximal Effect ◽  
Bacterial Isolates ◽  
Atypical Pathogens ◽  
Time Kill

ABSTRACT ABT-492 is a novel quinolone with potent activity against gram-positive, gram-negative, and atypical pathogens, making this compound an ideal candidate for the treatment of community-acquired pneumonia. We therefore compared the in vitro pharmacodynamic activity of ABT-492 to that of levofloxacin, an antibiotic commonly used for the treatment of pneumonia, through MIC determination and time-kill kinetic analysis. ABT-492 demonstrated potent activity against penicillin-sensitive, penicillin-resistant, and levofloxacin-resistant Streptococcus pneumoniae strains (MICs ranging from 0.0078 to 0.125 μg/ml); β-lactamase-positive and β-lactamase-negative Haemophilus influenzae strains (MICs ranging from 0.000313 to 0.00125 μg/ml); and β-lactamase-positive and β-lactamase-negative Moraxella catarrhalis strains (MICs ranging from 0.001 to 0.0025 μg/ml), with MICs being much lower than those of levofloxacin. Both ABT-492 and levofloxacin demonstrated concentration-dependent bactericidal activities in time-kill kinetics studies at four and eight times the MIC with 10 of 12 bacterial isolates exposed to ABT-492 and with 12 of 12 bacterial isolates exposed to levofloxacin. Sigmoidal maximal-effect models support concentration-dependent bactericidal activity. The model predicts that 50% of maximal activity can be achieved with concentrations ranging from one to two times the MIC for both ABT-492 and levofloxacin and that near-maximal activity (90% effective concentration) can be achieved at concentrations ranging from two to five times the MIC for ABT-492 and one to six times the MIC for levofloxacin.

Study of conformations of the adenosine phosphates. I: Adenosine monophosphate (AMP)

1980 ◽  
Vol 85 (2) ◽  
pp. 293-303 ◽  
Author(s):  
Sandra Zink ◽  
Charles L. Beckel ◽  
Allen C. Larson
Keyword(s):  
Adenosine Monophosphate ◽  
Adenosine Phosphates
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