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

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

scholarly journals Study of the Interaction of Sorption and Catalytic Centers in Carboxypeptidase T by X-ray Analysis

Crystals ◽  
2021 ◽  
Vol 11 (9) ◽  
pp. 1088
Author(s):  
Valerij Akparov ◽  
Vladimir Timofeev ◽  
Inna Kuranova ◽  
Ilias Khaliullin
Keyword(s):  
Substrate Specificity ◽  
Transition State ◽  
Kinetic Data ◽  
Carboxypeptidase B ◽  
Catalytic Center ◽  
X Ray ◽  
Thermoactinomyces Vulgaris ◽  
Distant Homolog ◽  
Carboxypeptidase T ◽  
Primary Specificity

Carboxypeptidase T (CPT; EC 3.4.17.18) from Thermoactinomyces vulgaris is a distant homolog of the highly specific pancreatic carboxypeptidase B; but has a broad substrate specificity; the source of which remains unclear. A previous study of the structural bases of the substrate specificity of CPT using stable sulfamoyl analogs of the transition state of the elimination of leucine; phenylalanine; arginine; and glutamic acid; showed that the binding of the C-terminal residue of the substrate to the primary selectivity pocket of CPT leads to a change in the distance between Zn2+ and the sulfur atom. This value is related to the efficiency of catalysis of the corresponding substrate or the inhibition constant of the corresponding stable analog of the transition state. In this work; we obtained crystallographic and kinetic data of the complex of CPT with N-sulfamoyl-L-valine; confirming the effect of the binding of the ligand’s side group by the primary specificity pocket of CPT on the structure of the catalytic center; which can explain the unusual substrate specificity of CPT.

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