Human α-Thrombin Inhibition by the Active Site Titrant Nα-(N,N-dimethylcarbamoyl)-α-azalysine p-nitrophenyl ester: A Comparative Kinetic and X-ray Crystallographic Study

1996 ◽  
Vol 258 (5) ◽  
pp. 851-859 ◽  
Author(s):  
Marco Nardini ◽  
Alessandra Pesce ◽  
Menico Rizzi ◽  
Elena Casale ◽  
Raffaella Ferraccioli ◽  
...  
Marine Drugs ◽  
2018 ◽  
Vol 16 (7) ◽  
pp. 240 ◽  
Author(s):  
Michael Groll ◽  
Henry Nguyen ◽  
Sreekumar Vellalath ◽  
Daniel Romo

Upon acylation of the proteasome by the β-lactone inhibitor salinosporamide A (SalA), tetrahydrofuran formation occurs by intramolecular alkylation of the incipient alkoxide onto the choroethyl sidechain and irreversibly blocks the active site. Our previously described synthetic approach to SalA, utilizing a bioinspired, late-stage, aldol-β-lactonization strategy to construct the bicyclic β-lactone core, enabled synthesis of (–)-homosalinosporamide A (homoSalA). This homolog was targeted to determine whether an intramolecular tetrahydropyran is formed in a similar manner to SalA. Herein, we report the X-ray structure of the yeast 20S proteasome:homoSalA-complex which reveals that tetrahydropyran ring formation does not occur despite comparable potency at the chymotrypsin-like active site in a luminogenic enzyme assay. Thus, the natural product derivative homoSalA blocks the proteasome by a covalent reversible mode of action, opening the door for further fine-tuning of proteasome inhibition.


1992 ◽  
Vol 1 (11) ◽  
pp. 1435-1446 ◽  
Author(s):  
Jeffrey W. Stebbins ◽  
Diane E. Robertson ◽  
Mary F. Roberts ◽  
Raymond C. Stevens ◽  
William N. Lipscomb ◽  
...  

2004 ◽  
Vol 69 (6) ◽  
pp. 1292-1300 ◽  
Author(s):  
Tahahiro Tani ◽  
Kazuki Sada ◽  
Masatsugu Ayabe ◽  
Yuya Iwashita ◽  
Takanori Kishida ◽  
...  

Crystal structure of hexylammonium anthracene-9-carboxylate was investigated. The salt was arranged by a one-dimensional hydrogen bond network to form a columnar structure in the crystalline state. This columnar structure should be the model of fibrous assemblies in the organogels of anthracene-9-carboxylate alkylammonium salts having a long alkyl chain.


1971 ◽  
Vol 246 (13) ◽  
pp. 4366-4368 ◽  
Author(s):  
Barbara W. Low ◽  
Reginald Potter ◽  
Richard B. Jackson ◽  
Nobuo Tamiya ◽  
Showbu Sato
Keyword(s):  
X Ray ◽  

The structure of yeast phosphoglycerate mutase determined by X-ray crystallographic and amino acid sequence studies has been interpreted in terms of the chemical, kinetic and mechanistic observations made on this enzyme. There are two histidine residues at the active site, with imidazole groups almost parallel to each other and approximately 0.4 nm apart, positioned close to the 2 and 3 positions of the substrate. The simplest interpretation of the available information suggests that a ping-pong type mechanism operates in which at least one of these histidine residues participates in the phosphoryl transfer reaction. The flexible C-terminal region also plays an important role in the enzymic reaction.


Sign in / Sign up

Export Citation Format

Share Document