Conformational compression and barrier height heterogeneity in the N-acetylglutamate kinase

The Journal of Physical Chemistry. B
Melchor Sanchez-MartinezRamon Crehuet


The role of motions in the catalytic cycle of an enzyme is the subject of much debate. Crystallographic results for the enzyme N-acetyl-l-glutamate kinase (NAGK), which is a suitable target for antibacterial drugs, suggest that a conformational compression of the active site favors catalysis. We have used a QM/MM scheme to compute energy profiles of the phosphoryl transfer reaction for 20 conformations of NAGK, starting from four crystal structures that represent different stages of the catalytic process. All paths show a common associative mechanism but with a wide range of barrier heights. The position of several active site residues and water molecules are found to determine the energetic barrier of each conformation, as revealed by principal component and partial least-squares chemometric analyses. In particular, conformations in which the two substrates have a shorter distance separation and a more linear mutual orientation tend to have lower energetic barriers, thus supporting the putative role of conformational compressive motions in catalysis. Interestingly, these motions are the same that lead to opening of the active site, which molecular dynamics simulations indicate is a fast process when the enzyme is free of subst...Continue Reading


Feb 1, 1996·Journal of Molecular Graphics·W HumphreyKlaus Schulten
Feb 23, 2002·Science·Elan Z EisenmesserDorothee Kern
Nov 4, 2005·Nature·Elan Z EisenmesserDorothee Kern
Dec 16, 2005·Proceedings of the National Academy of Sciences of the United States of America·Dror Tobi, Ivet Bahar
Dec 21, 2010·Biochimica Et Biophysica Acta·John D McGeaghAdrian J Mulholland
Apr 27, 2013·Chemical Reviews·Artur GoraJiri Damborsky

Related Concepts

N-acetyl-L-glutamate kinase
Alkalescens-Dispar Group
Quantum Theory
Rietveld Refinement
Phosphotransferases (Carboxyl Group Acceptor)
Crystallography, X-Ray
Principal Component Analysis
Molecular Dynamics

Trending Feeds


Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Synthetic Genetic Array Analysis

Synthetic genetic arrays allow the systematic examination of genetic interactions. Here is the latest research focusing on synthetic genetic arrays and their analyses.

Congenital Hyperinsulinism

Congenital hyperinsulinism is caused by genetic mutations resulting in excess insulin secretion from beta cells of the pancreas. Here is the latest research.

Neural Activity: Imaging

Imaging of neural activity in vivo has developed rapidly recently with the advancement of fluorescence microscopy, including new applications using miniaturized microscopes (miniscopes). This feed follows the progress in this growing field.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Epigenetic Memory

Epigenetic memory refers to the heritable genetic changes that are not explained by the DNA sequence. Find the latest research on epigenetic memory here.

Cell Atlas of the Human Eye

Constructing a cell atlas of the human eye will require transcriptomic and histologic analysis over the lifespan. This understanding will aid in the study of development and disease. Find the latest research pertaining to the Cell Atlas of the Human Eye here.

Femoral Neoplasms

Femoral Neoplasms are bone tumors that arise in the femur. Discover the latest research on femoral neoplasms here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.