Crystal structure and biochemical studies of Brucella melitensis 5′-methylthioadenosine/S-adenosylhomocysteine nucleosidase

2014 ◽  
Vol 446 (4) ◽  
pp. 965-970 ◽  
Author(s):  
Xusheng Kang ◽  
Yan Zhao ◽  
Daohua Jiang ◽  
Xuemei Li ◽  
Xianping Wang ◽  
...  
Keyword(s):  
Crystal Structure ◽  
Brucella Melitensis ◽  
Biochemical Studies

scholarly journals Structural and Biochemical Studies of Dihydrofolate Reductase from Streptococcus pyogenes as a Target for Antifolate Antibiotics

2018 ◽  
Author(s):  
Behnoush Hajian ◽  
Jolanta Krucinska ◽  
Michael Martins ◽  
Narendran G-Dayanan ◽  
Kishore Viswanathan ◽  
...  
Keyword(s):  
Crystal Structure ◽  
Streptococcus Pyogenes ◽  
Dihydrofolate Reductase ◽  
Wide Spectrum ◽  
Streptococcal Infections ◽  
Biochemical Studies ◽  
Live Bacteria ◽  
Dhfr Inhibitors ◽  
First Time ◽  
Structural Insights

ABSTRACTStreptococcus pyogenes, a beta-hemolytic bacterium, causes a wide spectrum of infections in human including pharyngitis, tonsillitis, scarlet fever, rheumatic fever, and necrotizing fasciitis. Streptococcal infections can also exist as co-infection with methicillin resistant Staphylococcus aureus (MRSA). Trimethoprim-sulfamethoxazole (TMP-SMX) combination has been used for treatment of S. pyogenes and MRSA co-infection. However, resistance to TMP, an inhibitor of dihydrofolate reductase enzyme (DHFR), has challenged the efficacy of TMP-SMX combination. We explored the activity of a series of novel DHFR inhibitors against S. pyogenes. This study identified potent inhibitors of DHFR enzyme from S. pyogenes with excellent inhibitory activity against the growth of the live bacteria. We determined, for the first time, the crystal structure of S. pyogenes DHFR which provides structural insights into design and development of antifolate agents against this global pathogen.

scholarly journals Structural and biochemical studies define Nudt12 as a new class of RNA deNADding enzyme in mammalian cells

2018 ◽  
Author(s):  
Ewa Grudzien-Nogalska ◽  
Yixuan Wu ◽  
Xinfu Jiao ◽  
Huijuan Cui ◽  
Ronald P. Hart ◽  
...  
Keyword(s):  
Crystal Structure ◽  
Molecular Basis ◽  
Mammalian Cells ◽  
Metabolic Stress ◽  
Cellular Metabolism ◽  
New Class ◽  
Mrna Targets ◽  
Biochemical Studies ◽  
Cellular Energetics ◽  
In Cells

ABSTRACTWe recently demonstrated mammalian cells harbor NAD-capped mRNAs that are hydrolyzed by the DXO deNADding enzyme. Here we report the Nudix protein Nudt12 is a second mammalian deNADding enzyme structurally and mechanistically distinct from DXO and targets different RNAs. Crystal structure of mouse Nudt12 in complex with the deNADding product AMP and three Mg2+ ions at 1.6 Å resolution provides exquisite insights into the molecular basis of the deNADding activity within the NAD pyrophosphate. Disruption of the Nudt12 gene stabilizes transfected NAD-capped RNA in cells and its endogenous NAD-capped mRNA targets are enriched in those encoding proteins involved in cellular energetics. Furthermore, exposure of cells to metabolic stress manifests changes in NAD-capped RNA levels indicating an association between NAD-capped RNAs and cellular metabolism. Lastly, we show that the bacterial RppH protein also possesses deNADding activity toward NAD-capped RNA but not free NAD, revealing a third class of deNADding enzymes.

scholarly journals Identification of the YEATS domain of GAS41 as a pH-dependent reader of histone succinylation

2018 ◽  
Vol 115 (10) ◽  
pp. 2365-2370 ◽  
Author(s):  
Yi Wang ◽  
Jing Jin ◽  
Matthew Wai Heng Chung ◽  
Ling Feng ◽  
Hongyan Sun ◽  
...  
Keyword(s):  
Crystal Structure ◽  
Posttranslational Modification ◽  
Salt Bridge ◽  
Histidine Residue ◽  
Binding Mechanism ◽  
Lysine Succinylation ◽  
Biochemical Studies ◽  
Ph Dependent ◽  
Carboxyl Terminal ◽  
Insight Into

Lysine succinylation is a newly discovered posttranslational modification with distinctive physical properties. However, to date rarely have studies reported effectors capable of interpreting this modification on histones. Following our previous study of SIRT5 as an eraser of succinyl-lysine (Ksuc), here we identified the GAS41 YEATS domain as a reader of Ksuc on histones. Biochemical studies showed that the GAS41 YEATS domain presents significant binding affinity toward H3K122suc upon a protonated histidine residue. Furthermore, cellular studies showed that GAS41 had prominent interaction with H3K122suc on histones and also demonstrated the coenrichment of GAS41 and H3K122suc on the p21 promoter. To investigate the binding mechanism, we solved the crystal structure of the YEATS domain of Yaf9, the GAS41 homolog, in complex with an H3K122suc peptide that demonstrated the presence of a salt bridge formed when a protonated histidine residue (His39) recognizes the carboxyl terminal of the succinyl group. We also solved the apo structure of GAS41 YEATS domain, in which the conserved His43 residue superimposes well with His39 in the Yaf9 structure. Our findings identified a reader of succinyl-lysine, and the binding mechanism will provide insight into the development of specific regulators targeting GAS41.

scholarly journals Crystal structure and biochemical studies of the trans-acting polyketide enoyl reductase LovC from lovastatin biosynthesis

2012 ◽  
Vol 109 (28) ◽  
pp. 11144-11149 ◽  
Author(s):  
B. D. Ames ◽  
C. Nguyen ◽  
J. Bruegger ◽  
P. Smith ◽  
W. Xu ◽  
...  
Keyword(s):  
Crystal Structure ◽  
Enoyl Reductase ◽  
Biochemical Studies

Crystal structure and biochemical studies of the bifunctional DNA primase-polymerase from phage NrS-1

2019 ◽  
Vol 510 (4) ◽  
pp. 573-579 ◽  
Author(s):  
Haojie Guo ◽  
Minjun Li ◽  
Tianle Wang ◽  
Hai Wu ◽  
Huan Zhou ◽  
...  
Keyword(s):  
Crystal Structure ◽  
Dna Primase ◽  
Biochemical Studies

scholarly journals C-terminal Redox Domain of Arabidopsis APR1 is a Non-Canonical Thioredoxin Domain with Glutaredoxin Function

Antioxidants ◽  
2019 ◽  
Vol 8 (10) ◽  
pp. 461 ◽  
Author(s):  
Chen ◽  
Chien ◽  
Cho ◽  
Chang ◽  
Hsu
Keyword(s):  
Crystal Structure ◽  
Vital Role ◽  
Terminal Domain ◽  
Biochemical Studies ◽  
Aps Reductase ◽  
Essential Nutrient ◽  
Sulfur Containing

Sulfur is an essential nutrient that can be converted into utilizable metabolic forms to produce sulfur-containing metabolites in plant. Adenosine 5′-phosphosulfate (APS) reductase (APR) plays a vital role in catalyzing the reduction of activated sulfate to sulfite, which requires glutathione. Previous studies have shown that the C-terminal domain of APR acts as a glutathione-dependent reductase. The crystal structure of the C-terminal redox domain of Arabidopsis APR1 (AtAPR1) shows a conserved α/β thioredoxin fold, but not a glutaredoxin fold. Further biochemical studies of the redox domain from AtAPR1 provided evidence to support the structural observation. Collectively, our results provide structural and biochemical information to explain how the thioredoxin fold exerts the glutaredoxin function in APR.

Crystal Structure Determination of Glycerol-Containing Lipids from Electron Diffraction Data. Use of Analog Compounds Based upon Configurational Isomers of Cyclopentane-1, 2, 3-TRIOL

1977 ◽  
Vol 35 ◽  
pp. 24-25
Author(s):  
Douglas L. Dorset ◽  
Anthony J. Hancock
Keyword(s):  
Crystal Structure ◽  
Electron Diffraction ◽  
Diffraction Data ◽  
Structure Determination ◽  
Crystal Surface ◽  
Coherent Scattering ◽  
Crystal Structure Determination ◽  
Electron Diffraction Data ◽  
Polar Group ◽  
Axis Orientation

Lipids containing long polymethylene chains were among the first compounds subjected to electron diffraction structure analysis. It was only recently realized, however, that various distortions of thin lipid microcrystal plates, e.g. bends, polar group and methyl end plane disorders, etc. (1-3), restrict coherent scattering to the methylene subcell alone, particularly if undistorted molecular layers have well-defined end planes. Thus, ab initio crystal structure determination on a given single uncharacterized natural lipid using electron diffraction data can only hope to identify the subcell packing and the chain axis orientation with respect to the crystal surface. In lipids based on glycerol, for example, conformations of long chains and polar groups about the C-C bonds of this moiety still would remain unknown.One possible means of surmounting this difficulty is to investigate structural analogs of the material of interest in conjunction with the natural compound itself. Suitable analogs to the glycerol lipids are compounds based on the three configurational isomers of cyclopentane-1,2,3-triol shown in Fig. 1, in which three rotameric forms of the natural glycerol derivatives are fixed by the ring structure (4-7).

Sign in / Sign up

Export Citation Format

Share Document