scholarly journals Cofactor-Mediated Conformational Dynamics Promote Product Release From Escherichia coli Dihydrofolate Reductase via an Allosteric Pathway

2015 ◽  
Vol 137 (29) ◽  
pp. 9459-9468 ◽  
Author(s):  
David Oyen ◽  
R. Bryn Fenwick ◽  
Robyn L. Stanfield ◽  
H. Jane Dyson ◽  
Peter E. Wright
Keyword(s):  
Escherichia Coli ◽  
Dihydrofolate Reductase ◽  
Conformational Dynamics ◽  
Product Release ◽  
Allosteric Pathway

scholarly journals Role of aspartate 27 in the binding of methotrexate to dihydrofolate reductase from Escherichia coli.

1988 ◽  
Vol 263 (19) ◽  
pp. 9187-9198 ◽  
Author(s):  
J R Appleman ◽  
E E Howell ◽  
J Kraut ◽  
M Kühl ◽  
R L Blakley
Keyword(s):  
Escherichia Coli ◽  
Dihydrofolate Reductase

How adding a single methylene to dihydrofolate reductase can change its conformational dynamics

2021 ◽  
Vol 154 (16) ◽  
pp. 165103
Author(s):  
Ryan W. Penhallurick ◽  
Alliyah Harold ◽  
Maya D. Durnal ◽  
Toshiko Ichiye
Keyword(s):  
Dihydrofolate Reductase ◽  
Conformational Dynamics

scholarly journals Crystal Structure of Escherichia coli Agmatinase: Catalytic Mechanism and Residues Relevant for Substrate Specificity

2021 ◽  
Vol 22 (9) ◽  
pp. 4769
Author(s):  
Pablo Maturana ◽  
María S. Orellana ◽  
Sixto M. Herrera ◽  
Ignacio Martínez ◽  
Maximiliano Figueroa ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Active Site ◽  
Catalytic Mechanism ◽  
Conformational Dynamics ◽  
High Specificity ◽  
Arginine Decarboxylase ◽  
Space Groups ◽  
X Ray Crystallography ◽  
High Dynamics ◽  
Dynamics Simulations

Agmatine is the product of the decarboxylation of L-arginine by the enzyme arginine decarboxylase. This amine has been attributed to neurotransmitter functions, anticonvulsant, anti-neurotoxic, and antidepressant in mammals and is a potential therapeutic agent for diseases such as Alzheimer’s, Parkinson’s, and cancer. Agmatinase enzyme hydrolyze agmatine into urea and putrescine, which belong to one of the pathways producing polyamines, essential for cell proliferation. Agmatinase from Escherichia coli (EcAGM) has been widely studied and kinetically characterized, described as highly specific for agmatine. In this study, we analyze the amino acids involved in the high specificity of EcAGM, performing a series of mutations in two loops critical to the active-site entrance. Two structures in different space groups were solved by X-ray crystallography, one at low resolution (3.2 Å), including a guanidine group; and other at high resolution (1.8 Å) which presents urea and agmatine in the active site. These structures made it possible to understand the interface interactions between subunits that allow the hexameric state and postulate a catalytic mechanism according to the Mn2+ and urea/guanidine binding site. Molecular dynamics simulations evaluated the conformational dynamics of EcAGM and residues participating in non-binding interactions. Simulations showed the high dynamics of loops of the active site entrance and evidenced the relevance of Trp68, located in the adjacent subunit, to stabilize the amino group of agmatine by cation-pi interaction. These results allow to have a structural view of the best-kinetic characterized agmatinase in literature up to now.

scholarly journals Methotrexate Binding to Dihydrofolate Reductase from a Methotrexate-resistant Strain of Escherichia coli

1973 ◽  
Vol 248 (18) ◽  
pp. 6375-6379
Author(s):  
Myra N. Williams ◽  
Martin Poe ◽  
Norma J. Greenfield ◽  
Jordan M. Hirshfield ◽  
Karst Hoogsteen
Keyword(s):  
Escherichia Coli ◽  
Dihydrofolate Reductase ◽  
Resistant Strain
Sign in / Sign up

Export Citation Format

Share Document