A model of the cyclophilin/cyclosporin A (CSA) complex from NMR and X-ray data suggests that CSA binds as a transition-state analog

1992 ◽  
Vol 114 (8) ◽  
pp. 3165-3166 ◽  
Author(s):  
S. W. Fesik ◽  
P. Neri ◽  
R. Meadows ◽  
E. T. Olejniczak ◽  
G. Gemmecker
Keyword(s):  
Transition State ◽  
Cyclosporin A ◽  
Transition State Analog ◽  
X Ray

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.

Molecular Basis of Chiral Acid Recognition by Candida rugosa Lipase: X-Ray Structure of Transition State Analog and Modeling of the Hydrolysis of Methyl 2-Methoxy-2-phenylacetate

2011 ◽  
Vol 353 (13) ◽  
pp. 2529-2544 ◽  
Author(s):  
Ian J. Colton ◽  
DeLu Tyler Yin ◽  
Pawel Grochulski ◽  
Romas J. Kazlauskas
Keyword(s):  
Transition State ◽  
Molecular Basis ◽  
Candida Rugosa ◽  
Candida Rugosa Lipase ◽  
Transition State Analog ◽  
X Ray ◽  
Hydrolysis Of

The X-ray Structure of a Transition State Analog Complex Reveals the Molecular Origins of the Catalytic Power and Substrate Specificity of Acetylcholinesterase

1996 ◽  
Vol 118 (10) ◽  
pp. 2340-2346 ◽  
Author(s):  
Michal Harel ◽  
Daniel M. Quinn ◽  
Haridasan K. Nair ◽  
Israel Silman ◽  
Joel L. Sussman
Keyword(s):  
Substrate Specificity ◽  
Transition State ◽  
Transition State Analog ◽  
X Ray ◽  
Catalytic Power

Design and synthesis of a transition state analog of a metalloporphyrin-catalysed oxidation reaction

2002 ◽  
Vol 06 (05) ◽  
pp. 362-365
Author(s):  
Rudolf Giger ◽  
Pascal Hoffmann
Keyword(s):  
Transition State ◽  
Cyclosporin A ◽  
Oxidation Reaction ◽  
Transition State Analog ◽  
Design And Synthesis ◽  
Catalysed Reaction ◽  
Catalysed Oxidation

A hapten that mimics the transition state of a metalloporphyrin-catalysed oxidation reaction was synthesized in order to generate antibodies that might be able to catalyse the regioselective metalloporphyrin-co-catalysed reaction of cyclosporin A to [D-Ser8]cyclosporin A.

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