scholarly journals Crystal Structure of Peptidyl-tRNA Hydrolase from <i>Acinetobacter baumannii</i> at 1.00 Å Resolution

2021 ◽  
Vol 9 (1) ◽  
pp. 13
Author(s):  
Vijayan Viswanathan ◽  
Pradeep Sharma ◽  
Prashant Kumar Singh ◽  
Punit Kaur ◽  
Sujata Sharma ◽  
...  
Keyword(s):  
Crystal Structure ◽  
Acinetobacter Baumannii

scholarly journals Active-Site Plasticity Is Essential to Carbapenem Hydrolysis by OXA-58 Class D β-Lactamase of Acinetobacter baumannii

2015 ◽  
Vol 60 (1) ◽  
pp. 75-86 ◽  
Author(s):  
Shivendra Pratap ◽  
Madhusudhanarao Katiki ◽  
Preet Gill ◽  
Pravindra Kumar ◽  
Dasantila Golemi-Kotra
Keyword(s):  
Crystal Structure ◽  
Acinetobacter Baumannii ◽  
Active Site ◽  
Active Sites ◽  
Multidrug Resistant ◽  
Crystal Structure Analysis ◽  
Content Type ◽  
Class D ◽  
Enzyme Species ◽  
Hydroxyethyl Group

ABSTRACTCarbapenem-hydrolyzing class D β-lactamases (CHDLs) are a subgroup of class D β-lactamases, which are enzymes that hydrolyze β-lactams. They have attracted interest due to the emergence of multidrug-resistantAcinetobacter baumannii, which is not responsive to treatment with carbapenems, the usual antibiotics of choice for this bacterium. Unlike other class D β-lactamases, these enzymes efficiently hydrolyze carbapenem antibiotics. To explore the structural requirements for the catalysis of carbapenems by these enzymes, we determined the crystal structure of the OXA-58 CHDL ofA. baumanniifollowing acylation of its active-site serine by a 6α-hydroxymethyl penicillin derivative that is a structural mimetic for a carbapenem. In addition, several point mutation variants of the active site of OXA-58, as identified by the crystal structure analysis, were characterized kinetically. These combined studies confirm the mechanistic relevance of a hydrophobic bridge formed over the active site. This structural feature is suggested to stabilize the hydrolysis-productive acyl-enzyme species formed from the carbapenem substrates of this enzyme. Furthermore, our structural studies provide strong evidence that the hydroxyethyl group of carbapenems samples different orientations in the active sites of CHDLs, and the optimum orientation for catalysis depends on the topology of the active site allowing proper closure of the active site. We propose that CHDLs use the plasticity of the active site to drive the mechanism of carbapenem hydrolysis toward efficiency.

scholarly journals Crystal structure of tripartite-type ABC transporter MacB from Acinetobacter baumannii

2017 ◽  
Vol 8 (1) ◽  
Author(s):  
Ui Okada ◽  
Eiki Yamashita ◽  
Arthur Neuberger ◽  
Mayu Morimoto ◽  
Hendrik W. van Veen ◽  
...  
Keyword(s):  
Crystal Structure ◽  
Acinetobacter Baumannii ◽  
Abc Transporter

scholarly journals Crystal Structures of Pyrophosphatase from Acinetobacter baumannii: Snapshots of Pyrophosphate Binding and Identification of a Phosphorylated Enzyme Intermediate

2019 ◽  
Vol 20 (18) ◽  
pp. 4394
Author(s):  
Yunlong Si ◽  
Xing Wang ◽  
Guosong Yang ◽  
Tong Yang ◽  
Yuying Li ◽  
...  
Keyword(s):  
Crystal Structure ◽  
Water Molecule ◽  
Acinetobacter Baumannii ◽  
Divalent Cations ◽  
Wild Type ◽  
Wild Type Enzyme ◽  
Catalytic Center ◽  
Favorable Reaction ◽  
Enzyme Intermediate

All living things have pyrophosphatases that hydrolyze pyrophosphate and release energy. This energetically favorable reaction drives many energetically unfavorable reactions. An accepted catalytic model of pyrophosphatase shows that a water molecule activated by two divalent cations (M1 and M2) within the catalytic center can attack pyrophosphate in an SN2 mechanism and thus hydrolyze the molecule. However, our co-crystal structure of Acinetobacter baumannii pyrophosphatase with pyrophosphate shows that a water molecule from the solvent may, in fact, be the actual catalytic water. In the co-crystal structure of the wild-type pyrophosphatase with pyrophosphate, the electron density of the catalytic centers of each monomer are different from one another. This indicates that pyrophosphates in the catalytic center are dynamic. Our mass spectroscopy results have identified a highly conserved lysine residue (Lys30) in the catalytic center that is phosphorylated, indicating that the enzyme could form a phosphoryl enzyme intermediate during hydrolysis. Mutation of Lys30 to Arg abolished the activity of the enzyme. In the structure of the apo wild type enzyme, we observed that a Na+ ion is coordinated by residues within a loop proximal to the catalytic center. Therefore, we mutated three key residues within the loop (K143R, P147G, and K149R) and determined Na+ and K+-induced inhibition on their activities. Compared to the wild type enzyme, P147G is most sensitive to these cations, whereas K143R was inactive and K149R showed no change in activity. These data indicate that monovalent cations could play a role in down-regulating pyrophosphatase activity in vivo. Overall, our results reveal new aspects of pyrophosphatase catalysis and could assist in the design of specific inhibitors of Acinetobacter baumannii growth.

scholarly journals Crystal structure of a UDP-GlcNAc epimerase for surface polysaccharide biosynthesis in Acinetobacter baumannii

PLoS ONE ◽  
2018 ◽  
Vol 13 (1) ◽  
pp. e0191610
Author(s):  
Bhumika S. Shah ◽  
Heather E. Ashwood ◽  
Stephen J. Harrop ◽  
Daniel N. Farrugia ◽  
Ian T. Paulsen ◽  
...  
Keyword(s):  
Crystal Structure ◽  
Acinetobacter Baumannii ◽  
Polysaccharide Biosynthesis ◽  
Surface Polysaccharide

scholarly journals Molecular basis of dimerization of lytic transglycosylase revealed by the crystal structure of MltA from Acinetobacter baumannii

IUCrJ ◽  
2021 ◽  
Vol 8 (6) ◽  
Author(s):  
Hyunseok Jang ◽  
Hackwon Do ◽  
Chang Min Kim ◽  
Gi Eob Kim ◽  
Jun Hyuck Lee ◽  
...  
Keyword(s):  
Crystal Structure ◽  
Acinetobacter Baumannii ◽  
Outer Membrane ◽  
Bacterial Cells ◽  
Working Mechanism ◽  
Lytic Transglycosylase ◽  
Membrane Bound ◽  
Bacterial Outer Membrane ◽  
Related Proteins ◽  
Critical Process

Peptidoglycan digestion by murein-degrading enzymes is a critical process in bacterial cell growth and/or cell division. The membrane-bound lytic murein transglycosylase A (MltA) is a murein-degrading enzyme; it catalyzes the cleavage of the β-1,4-glycosidic linkage between N-acetylmuramic acid and N-acetylglucosamine in peptidoglycans. Although substrate recognition and cleavage by MltA have been examined by previous structural and mutagenesis studies, the overall mechanism of MltA in conjunction with other functionally related molecules on the outer membrane of bacterial cells for peptidoglycan degradation has remained elusive. In this study, the crystal structure of MltA from the virulent human pathogen Acinetobacter baumannii is characterized and presented. The study indicated that MltA from A. baumannii forms homodimers via an extra domain which is specific to this species. Furthermore, the working mechanism of MltA with various functionally related proteins on the bacterial outer membrane was modeled based on the structural and biochemical analysis.

scholarly journals Crystal Structure of the putative tail fiber protein gp53 from the Acinetobacter baumannii bacteriophage AP22

2019 ◽  
Author(s):  
Lada V. Sycheva ◽  
Mikhail M. Shneider ◽  
Anastasia V. Popova ◽  
Rustam H. Ziganshin ◽  
Nikolay V. Volozhantsev ◽  
...  
Keyword(s):  
Crystal Structure ◽  
Ethylene Glycol ◽  
Acinetobacter Baumannii ◽  
Host Cell ◽  
Infection Process ◽  
Tail Fiber ◽  
Lytic Bacteriophage ◽  
Cell Binding ◽  
Tail Fiber Protein ◽  
Fiber Protein

AbstractThis report describes the structure of a putative tail fiber protein of the Acinetobacter baumannii bacteriophage AP22. The target host range of strictly lytic bacteriophage AP22 includes many clinical isolates of A. baumannii from hospitals in Chelyabinsk, Nizhny Novgorod, Moscow and St. Petersburg (Russia), but its host cell binding apparatus remains uncharacterized. Here, we report the crystal structure of the C-terminal fragment of AP22 gene product 53 (gp53) one of its two putative host cell-binding proteins. We show that gp53 forms a trimeric fiber and binds ethylene glycol and glycerol molecules that represent known surrogates of the oligosaccharide backbone. However, despite its structural similarities to other phage/virus host cell-binding fibers and its binding to small sugar-like molecules, gp53 did not inhibit AP22 infection and its role in the infection process remains unclear.

scholarly journals Targeting Omp-A Protein of Acinetobacter Baumannii with the Bio-Active Compounds from Azadirachta Indica - an in-silico Approach

2021 ◽  
pp. 323-334
Author(s):  
R. Nandita ◽  
A. S. Smiline Girija ◽  
P. Sankar Ganesh ◽  
J. Vijayashree Priyadharsini
Keyword(s):  
Crystal Structure ◽  
Acinetobacter Baumannii ◽  
Azadirachta Indica ◽  
In Silico ◽  
3D Structure ◽  
Data Bank ◽  
Binding Energies ◽  
Active Compounds ◽  
Discovery Studio ◽  
Ompa Protein

Background: Acinetobacter baumannii is a gram negative bacterium which is typically short, round, coccobacillus and was named after the bacteriologist Paul Baumann. It is an emerging dental pathogen since it acquires  drug resistance and expression of several virulence genes. It is an opportunistic pathogen in humans, affecting people with compromised immune systems. Acinetobacter baumannii is an arising nosocomial microorganism causing serious complications because of the propensity of its multi-drug resistant property. Aim: The aim of the present study was to target omp-A protein of Acinetobacter baumannii with the bio active compounds from Azadirachta indica an in-silico approach. Materials and Methods: The crystal structure of ompA protein was obtained from the PDB protein data bank. The structures of the bio-active derivatives of A. indica were obtained from the chemsketch software. The generated 3D structures were then optimised. Auto Dock instrument was utilized for docking investigation to interpret the affinity between bio-compounds of A. indica against ompA protein of A. baumannii. Results: The 3D crystal structure of OmpA-like domain from A.baumannii was retrieved from PDB database and its PDB ID was 3TD3 – A chain. 3D Structure of OmpA visualization using Biovia-Discovery studio visualizer. The 2D structure of compounds from Azadirachta indica was drawn using ACD chemsketch and saved in MDL-mol format and converted to PDB format using open babel converter. The final docked structures for the drug ligand interactions were assessed for their binding energies and hydrogen bonds. Conclusion: The present study had achieved the anti-biofilm inhibitory effect of imidazole-2-carboxylic acid from A. indica exhibiting a great interaction between activity with ompA utilizing computational investigation.

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