On the rational design of renin inhibitors: x-ray studies of aspartic proteinases complexed with transition-state analogs

Biochemistry ◽  
1987 ◽  
Vol 26 (18) ◽  
pp. 5585-5590 ◽  
Author(s):  
T. L. Blundell ◽  
J. Cooper ◽  
S. I. Foundling ◽  
D. M. Jones ◽  
B. Atrash ◽  
...  
Keyword(s):  
Transition State ◽  
Rational Design ◽  
Aspartic Proteinases ◽  
X Ray ◽  
Renin Inhibitors ◽  
Transition State Analogs

Rational design, synthesis, and X-ray structure of renin inhibitors with extended P1 sidechains

1995 ◽  
Vol 5 (22) ◽  
pp. 2623-2626 ◽  
Author(s):  
Bruce A. Lefker ◽  
William A. Hada ◽  
Ann S. Wright ◽  
William H. Martin ◽  
Ingrid A. Stock ◽  
...  
Keyword(s):  
Rational Design ◽  
Design Synthesis ◽  
X Ray ◽  
Renin Inhibitors

An allolactose trapped at the lacZ β-galactosidase active site with its galactosyl moiety in a 4H3 conformation provides insights into the formation, conformation, and stabilization of the transition state

2015 ◽  
Vol 93 (6) ◽  
pp. 531-540 ◽  
Author(s):  
Robert W. Wheatley ◽  
Reuben E. Huber
Keyword(s):  
Transition State ◽  
Active Site ◽  
Axial Position ◽  
Transition State Analog ◽  
X Ray ◽  
Transition State Analogs ◽  
Leaving Group ◽  
Sugar Ring ◽  
Oxocarbenium Ion ◽  
Ring Distortion

When lactose was incubated with G794A-β-galactosidase (a variant with a “closed” active site loop that binds transition state analogs well) an allolactose was trapped with its Gal moiety in a 4H3 conformation, similar to the oxocarbenium ion-like conformation expected of the transition state. The numerous interactions formed between the 4H3 structure and β-galactosidase indicate that this structure is representative of the transition state. This conformation is also very similar to that of d-galactono-1,5-lactone, a good transition state analog. Evidence indicates that substrates take up the 4H3 conformation during migration from the shallow to the deep mode. Steric forces utilizing His418 and other residues are important for positioning the O1 leaving group into a quasi-axial position. An electrostatic interaction between the O5 of the distorted Gal and Tyr503 as well as C–H–π bonds with Trp568 are also significant. Computational studies of the energy of sugar ring distortion show that the β-galactosidase reaction itinerary is driven by energetic considerations in utilization of a 4H3 transition state with a novel 4C1-4H3-4C1 conformation itinerary. To our knowledge, this is the first X-ray crystallographic structural demonstration that the transition state of a natural substrate of a glycosidase has a 4H3 conformation.

Renin inhibitors. Design of angiotensinogen transition-state analogs containing novel (2R,3R,4R,5S)-5-amino-3,4-dihydroxy-2-isopropyl-7-methyloctanoic acid

1987 ◽  
Vol 30 (6) ◽  
pp. 976-982 ◽  
Author(s):  
Suvit Thaisrivongs ◽  
Donald T. Pals ◽  
Lisa T. Kroll ◽  
Steve R. Turner ◽  
Fu Son Han
Keyword(s):  
Transition State ◽  
Renin Inhibitors ◽  
Transition State Analogs

scholarly journals Rational Design of Ag/ZnO Hybrid Nanoparticles on Sericin/Agarose Composite Film for Enhanced Antimicrobial Applications

2020 ◽  
Vol 22 (1) ◽  
pp. 105
Author(s):  
Wanting Li ◽  
Zixuan Huang ◽  
Rui Cai ◽  
Wan Yang ◽  
Huawei He ◽  
...  
Keyword(s):  
Mechanical Properties ◽  
Antimicrobial Activity ◽  
Composite Film ◽  
Water Absorption ◽  
Rational Design ◽  
Hybrid Nanoparticles ◽  
Gram Negative Bacteria ◽  
Gram Positive ◽  
Gram Negative ◽  
X Ray

Silver-based hybrid nanomaterials are receiving increasing attention as potential alternatives for traditional antimicrobial agents. Here, we proposed a simple and eco-friendly strategy to efficiently assemble zinc oxide nanoparticles (ZnO) and silver nanoparticles (AgNPs) on sericin-agarose composite film to impart superior antimicrobial activity. Based on a layer-by-layer self-assembly strategy, AgNPs and ZnO were immobilized on sericin-agarose films using the adhesion property of polydopamine. Scanning electron microscopy, energy-dispersive X-ray spectroscopy, and X-ray powder diffraction spectroscopy were used to show the morphology of AgNPs and ZnO on the surface of the composite film and analyze the composition and structure of AgNPs and ZnO, respectively. Water contact angle, swelling ratio, and mechanical property were determined to characterize the hydrophilicity, water absorption ability, and mechanical properties of the composite films. In addition, the antibacterial activity of the composite film was evaluated against Gram-positive and Gram-negative bacteria. The results showed that the composite film not only has desirable hydrophilicity, high water absorption ability, and favorable mechanical properties but also exhibits excellent antimicrobial activity against both Gram-positive and Gram-negative bacteria. It has shown great potential as a novel antimicrobial biomaterial for wound dressing, artificial skin, and tissue engineering.

Sign in / Sign up

Export Citation Format

Share Document