Structure and Function of the Xenobiotic Substrate Binding Site of a Glutathione S-Transferase as Revealed by X-ray Crystallographic Analysis of Product Complexes with the Diastereomers of 9-(S-Glutathionyl)-10-hydroxy-9,10-dihydrophenanthrene

Biochemistry ◽  
1994 ◽  
Vol 33 (5) ◽  
pp. 1043-1052 ◽  
Author(s):  
Xinhua Ji ◽  
William W. Johnson ◽  
Muctarr A. Sesay ◽  
Laura Dickert ◽  
Satya M. Prasad ◽  
...  
Keyword(s):  
Binding Site ◽  
Substrate Binding ◽  
Crystallographic Analysis ◽  
Structure And Function ◽  
Glutathione S Transferase ◽  
Substrate Binding Site ◽  
X Ray ◽  
And Function

Structure and Function of the Xenobiotic Substrate-Binding Site and Location of a Potential Non-Substrate-Binding Site in a Class π GlutathioneS-Transferase†,‡

Biochemistry ◽  
1997 ◽  
Vol 36 (32) ◽  
pp. 9690-9702 ◽  
Author(s):  
Xinhua Ji ◽  
Maria Tordova ◽  
Rosemary O'Donnell ◽  
James F. Parsons ◽  
Janet B. Hayden ◽  
...  
Keyword(s):  
Binding Site ◽  
Substrate Binding ◽  
Structure And Function ◽  
Substrate Binding Site ◽  
And Function

Structure and Function of Residue 104 and Water Molecules in the Xenobiotic Substrate-Binding Site in Human GlutathioneS-Transferase P1-1†,‡

Biochemistry ◽  
1999 ◽  
Vol 38 (32) ◽  
pp. 10231-10238 ◽  
Author(s):  
Xinhua Ji ◽  
Jaroslaw Blaszczyk ◽  
Bing Xiao ◽  
Rosemary O'Donnell ◽  
Xun Hu ◽  
...  
Keyword(s):  
Binding Site ◽  
Substrate Binding ◽  
Structure And Function ◽  
Water Molecules ◽  
Substrate Binding Site ◽  
And Function

scholarly journals In-silico Investigation of the Interaction between Beta-class Glutathione S-Transferase and Five Antibiotics, namely; Ampicillin, Tetracycline, Chloramphenicol, Ciprofloxacin and Cephalexin

2021 ◽  
Vol 25 (4) ◽  
pp. 497-502
Author(s):  
D. Shehu ◽  
S Danlami ◽  
M. Ya’u ◽  
A. Babandi ◽  
H.M. Yakasai ◽  
...  
Keyword(s):  
Amino Acids ◽  
Antibiotic Resistance ◽  
Molecular Docking ◽  
Binding Site ◽  
Substrate Binding ◽  
Docking Study ◽  
Glutathione S Transferase ◽  
Molecular Docking Study ◽  
Substrate Binding Site ◽  
Glutathione S Transferases

Glutathione s-transferases(GSTs) are enzymes involved in the conjugation and deactivation of various xenobiotics including drugs. Thisin-silico study was undertaken in order to investigate the interaction between beta-class glutathione s-transferase and five selected antibiotics, namely; ampicillin, tetracycline, chloramphenicol, ciprofloxacin and cephalexin using molecular docking study. RaptorX server was used to predict the amino acids involved at the binding sitewhile molecular docking study was employed in order to investigate the binding interactions.RaptorX predicted several amino acids which were different from the ones observed in molecular docking because of the variability in the substrate binding site of GSTs however, all the amino acids predicted by RaptorX were also found to be involved in the GSH binding.Lys107, Phe109, Ser110, Leu113, Trp114, His115 and Arg123, Leu168 were the amino acids involved in the binding of various antibiotics to the substrate binding site of the protein while Ala9, Cys10, Leu32, Tyr51, Val52, Pro53, Glu65 and Ala66were involved in the binding of the co-substrate GSH to the binding site of the protein. The results indicated that all the antibiotics showed a good binding affinity with the beta class GST and are therefore capable of deactivating the drugs. With these, finding a beta class GST inhibitors alongside antibiotics during a treatment of diseases will be of beneficial in the current fight against antibiotic resistance.

scholarly journals Molecular recognition of sugar binding in a melibiose transporter MelB by X-ray crystallography

2020 ◽  
Author(s):  
Lan Guan ◽  
Parameswaran Hariharan
Keyword(s):  
Molecular Recognition ◽  
Binding Site ◽  
Crystal Structures ◽  
Mammalian Cells ◽  
Substrate Binding ◽  
Structural Basis ◽  
Cooperative Binding ◽  
Recognition Mechanism ◽  
Substrate Binding Site ◽  
X Ray

AbstractThe symporter melibiose permease MelB is the best-studied representative from MFS_2 family and the only protein in this large family with crystal structure determined. Previous thermodynamic studies show that MelB utilizes a cooperative binding as the core mechanism for its obligatory symport. Here we present two sugar-bound X-ray crystal structures of a Salmonella typhimurium MelB D59C uniport mutant that binds and catalyzes melibiose transport uncoupled to either cation, as determined by biochemical and biophysical characterizations. The two structures with bound nitrophenyl-α-D-galactoside or dodecyl-β-D-melibioside, which were refined to a resolution of 3.05 or 3.15 Å, respectively, are virtually identical at an outward-facing conformation; each one contains a α-galactoside molecule in the middle of protein. In the substrate-binding site, the galactosyl moiety on both ligands are at an essentially same configuration, so a galactoside specificity determinant pocket can be recognized, and hence the molecular recognition mechanism for the binding of sugar in MelB is deciphered. The data also allow to assign the conserved cation-binding pocket, which is directly connected to the sugar specificity determinant pocket. The intimate connection between the two selection sites lays the structural basis for the cooperative binding and coupled transport. This key structural finding answered the long-standing question on the substrate binding for the Na+-coupled MFS family of transporters.SignificanceMajor facilitator superfamily_2 transporters contain >10,000 members that are widely expressed from bacteria to mammalian cells, and catalyze uptake of varied nutrients from sugars to phospholipids. While several crystal structures with bound sugar for other MFS permeases have been determined, they are either uniporters or symporters coupled solely to H+. MelB catalyzes melibiose symport with either Na+, Li+, or H+, a prototype for Na+-coupled MFS transporters, but its sugar recognition has been a long-unsolved puzzle. Two high-resolution crystal structures presented here clearly reveal the molecular recognition mechanism for the binding of sugar in MelB. The substrate-binding site is characterized with a small specificity groove adjoining a large nonspecific cavity, which could offer a potential for future exploration of active transporters for drug delivery.

Wucherria bancrofti glutathione S-Transferase: Insights into the 2.3 Å resolution X-ray structure and function, a therapeutic target for human lymphatic filariasis

2018 ◽  
Vol 505 (4) ◽  
pp. 979-984
Author(s):  
Prince Rajaiah Prabhu ◽  
Sakthi Devi Moorthy ◽  
Jayaprakasam Madhumathi ◽  
Satya Narayan Pradhan ◽  
Markus Perbandt ◽  
...  
Keyword(s):  
Lymphatic Filariasis ◽  
Therapeutic Target ◽  
Structure And Function ◽  
Glutathione S Transferase ◽  
X Ray ◽  
And Function

scholarly journals Mechanism of Tissue Factor Activation on HL-60 Cells

Blood ◽  
1997 ◽  
Vol 89 (9) ◽  
pp. 3270-3276 ◽  
Author(s):  
Ronald R. Bach ◽  
Charles F. Moldow
Keyword(s):  
Binding Site ◽  
Tissue Factor ◽  
Quaternary Structure ◽  
Factor Viia ◽  
Calcium Ionophore ◽  
Structure And Function ◽  
Cross Linking ◽  
Substrate Binding Site ◽  
Pseudosubstrate Inhibitors ◽  
And Function

AbstractTissue factor (TF ) procoagulant activity (PCA) on the surface of intact HL-60 cells is encrypted. This latent TF PCA was activated by exposing the cells to ionomycin, a calcium ionophore. Within seconds an increase in TF PCA of greater than 100-fold was observed. The ionomycin effect was blocked by pretreating the cells with calmidazolium, a calmodulin inhibitor. Changes in TF structure and function, coincident with the ionophore-induced increase in TF PCA, were identified. TF-factor VIIa complexes formed on both untreated and ionophore-treated cells, but pseudosubstrate inhibitors only bound to TF-factor VIIa on the ionophore-treated cells. TF PCA was inhibited by reacting cells with sulfosuccinimidyl-6-(biotinamido)hexanoate, and the rate of this reaction increased twofold after cells were exposed to ionomycin. When proteins on the surface of untreated cells, expressing minimal TF PCA, were cross-linked with 3-3′-dithiobis(sulfosuccinimidylpropionate), cross-linked TF dimers were produced. TF cross-linking was prevented by first treating the cells with ionomycin. These results suggest a mechanism for the ionomycin-induced increase in TF PCA. TF activation appears to be a calmodulin-dependent process, which exposes an essential macromolecular substrate binding site on TF, possibly as the result of a change in TF quaternary structure.

scholarly journals Synthesis of rigidified flavin–guanidinium ion conjugates and investigation of their photocatalytic properties

2009 ◽  
Vol 5 ◽  
Author(s):  
Harald Schmaderer ◽  
Mouchumi Bhuyan ◽  
Burkhard König
Keyword(s):  
Binding Site ◽  
Redox Reactions ◽  
Substrate Binding ◽  
Alder Reaction ◽  
Benzyl Ester ◽  
Diels Alder ◽  
Substrate Binding Site ◽  
X Ray ◽  
Diels Alder Reaction ◽  
Acid Structure

Flavin chromophores can mediate redox reactions upon irradiation by blue light. In an attempt to increase their catalytic efficacy, flavin derivatives bearing a guanidinium ion as oxoanion binding site were prepared. Chromophore and substrate binding site are linked by a rigid Kemp’s acid structure. The molecular structure of the new flavins was confirmed by an X-ray structure analysis and their photocatalytic activity was investigated in benzyl ester cleavage, nitroarene reduction and a Diels–Alder reaction. The modified flavins photocatalyze the reactions, but the introduced substrate binding site does not enhance their performance.

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