Stochastic boundary molecular dynamics simulation of L-ribose in the active site of Actinoplanes missouriensis xylose isomerase and its Val135Asn mutant with improved reaction rate

Biochimica Et Biophysica Acta
Harri SantaOssi Turunen


We used molecular dynamics simulations to study how a non-natural substrate, L-ribose, interacts with the active site of Actinoplanes missouriensis xylose isomerase. The simulations showed that L-ribose does not stay liganded in the active site in the same way as D-xylose, in which the oxygens O2 and O4 are liganded to the metal M1. The oxygen O4 of L-ribose moved away from the metal M1 to an upside down position. Furthermore, the distances of the carbons C1 and C2 of L-ribose to the catalytic metal M2 were higher than in the case of D-xylose. These findings explain the extremely low reaction rate of xylose isomerase with L-ribose. The mutation V135N close to the C5-OH of the substrate increased the reaction efficiency 2- to 4-fold with L-ribose. V135N did not affect the reaction with D-xylose and L-arabinose, whereas the reaction with D-glucose was impaired, probably due to a hydrogen bond between Asn-135 and the substrate. When L-ribose was the substrate, Asn-135 formed a hydrogen bond to Glu-181. As a consequence, O4 of L-ribose stayed liganded to the metal M1 in the V135N mutant in molecular dynamics simulations. This explains the decreased K(m) of the V135N mutant with L-ribose.


May 1, 1991·Proceedings of the National Academy of Sciences of the United States of America·M MengJ G Zeikus
Mar 1, 1990·Journal of Molecular Graphics·G Vriend
Aug 1, 1985·Biophysical Chemistry·Y B Tewari, R N Goldberg
Sep 29, 1995·The Journal of Biological Chemistry·R D WhitakerC A Batt
Sep 15, 1988·Physical Review A: General Physics·A D Becke
Oct 10, 2002·Current Protein & Peptide Science·B Asboth, G Náray-Szabó
Dec 24, 2002·Journal of Computational Chemistry·Mireia Garcia-VilocaJiali Gao
Feb 17, 2005·Protein Engineering, Design & Selection : PEDS·Johanna KarimäkiOssi Turunen


Jan 23, 2009·Applied Microbiology and Biotechnology·Ran-Young YoonDeok-Kun Oh
Mar 7, 2013·Applied Microbiology and Biotechnology·Hajer Ben HlimaNushin Aghajari
Nov 6, 2008·Journal of Biotechnology·Ran-Young YoonDeok-Kun Oh
Oct 13, 2020·The Protein Journal·Huri BulutBaris Binay

Related Concepts

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.

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.

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.

Hereditary Sensory Autonomic Neuropathy

Hereditary Sensory Autonomic Neuropathies are a group of inherited neurodegenerative disorders characterized clinically by loss of sensation and autonomic dysfunction. Here is the latest research on these neuropathies.

Spatio-Temporal Regulation of DNA Repair

DNA repair is a complex process regulated by several different classes of enzymes, including ligases, endonucleases, and polymerases. This feed focuses on the spatial and temporal regulation that accompanies DNA damage signaling and repair enzymes and processes.

Glut1 Deficiency

Glut1 deficiency, an autosomal dominant, genetic metabolic disorder associated with a deficiency of GLUT1, the protein that transports glucose across the blood brain barrier, is characterized by mental and motor developmental delays and infantile seizures. Follow the latest research on Glut1 deficiency with this feed.

Separation Anxiety

Separation anxiety is a type of anxiety disorder that involves excessive distress and anxiety with separation. This may include separation from places or people to which they have a strong emotional connection with. It often affects children more than adults. Here is the latest research on separation anxiety.

KIF1A Associated Neurological Disorder

KIF1A associated neurological disorder (KAND) is a rare neurodegenerative condition caused by mutations in the KIF1A gene. KAND may present with a wide range and severity of symptoms including stiff or weak leg muscles, low muscle tone, a lack of muscle coordination and balance, and intellectual disability. Find the latest research on KAND here.

Regulation of Vocal-Motor Plasticity

Dopaminergic projections to the basal ganglia and nucleus accumbens shape the learning and plasticity of motivated behaviors across species including the regulation of vocal-motor plasticity and performance in songbirds. Discover the latest research on the regulation of vocal-motor plasticity here.