Table of Contents: June 2015

This is a handmade painting of the membrane-bound fatty acid amide hydrolase (FAAH), a key enzyme for the endocannabinoid lipid signaling pathway that hydrolyzes a variety of lipids with different catalytic rates. Through the integration of microsecond-long molecular dynamics simulations with mutagenesis and kinetic experiments, Palermo et al. describe a novel mechanism and mechanistic features for lipid selection in FAAH.

Key contributions include exploitation of structural flexibility, gating residues and multiple cavities in one catalytic site to selectively hydrolyze the main substrate anandamide. Palermo et al. also discuss how this structural framework could likely be a general enzymatic strategy of other lipiddegrading enzymes to select the preferred lipid substrate within a broad spectrum of biologically active lipids.

These findings encourage additional experimental verifications of the role of ligand and structural flexibility for lipid-selection in several other lipid-degrading enzymes.

Image Credit: Painting by Giulia Palermo with digital manipulation by O'Reilly Science Art, LLC


Messages from ISCB

Computational Biology: Moving into the Future One Click at a Time

Christiana N. Fogg, Diane E. Kovats

2015 ISCB Overton Prize Awarded to Curtis Huttenhower

Christiana N. Fogg, Diane E. Kovats

ISMB/ECCB Rebooted: 2015 Brings Major Update to the Meeting Program

Christiana N. Fogg, Diane E. Kovats

Research Articles

Rational Design and Adaptive Management of Combination Therapies for Hepatitis C Virus Infection

Ruian Ke, Claude Loverdo, Hangfei Qi, Ren Sun, James O. Lloyd-Smith

Spatio-temporal Dynamics and Mechanisms of Stress Granule Assembly

Daisuke Ohshima, Kyoko Arimoto-Matsuzaki, Taichiro Tomida, Mutsuhiro Takekawa, Kazuhisa Ichikawa

Keys to Lipid Selection in Fatty Acid Amide Hydrolase Catalysis: Structural Flexibility, Gating Residues and Multiple Binding Pockets

Giulia Palermo, Inga Bauer, Pablo Campomanes, Andrea Cavalli, Andrea Armirotti, Stefania Girotto, Ursula Rothlisberger, Marco De Vivo

The Decay of Motor Memories Is Independent of Context Change Detection

Andrew E. Brennan, Maurice A. Smith

A Computational, Tissue-Realistic Model of Pressure Ulcer Formation in Individuals with Spinal Cord Injury

Cordelia Ziraldo, Alexey Solovyev, Ana Allegretti, Shilpa Krishnan, M. Kristi Henzel, Gwendolyn A. Sowa, David Brienza, Gary An, Qi Mi, Yoram Vodovotz

Antibiotic Restriction Might Facilitate the Emergence of Multi-drug Resistance

Uri Obolski, Gideon Y. Stein, Lilach Hadany

Antenna Mechanism of Length Control of Actin Cables

Lishibanya Mohapatra, Bruce L. Goode, Jane Kondev

Related Articles

  1. Correction: Antenna Mechanism of Length Control of Actin Cables

Emerging Object Representations in the Visual System Predict Reaction Times for Categorization

J. Brendan Ritchie, David A. Tovar, Thomas A. Carlson

BASiCS: Bayesian Analysis of Single-Cell Sequencing Data

Catalina A. Vallejos, John C. Marioni, Sylvia Richardson

Integration of Metabolic and Quorum Sensing Signals Governing the Decision to Cooperate in a Bacterial Social Trait

Kerry E. Boyle, Hilary Monaco, Dave van Ditmarsch, Maxime Deforet, Joao B. Xavier

Inference of Network Dynamics and Metabolic Interactions in the Gut Microbiome

Steven N. Steinway, Matthew B. Biggs, Thomas P. Loughran Jr, Jason A. Papin, Reka Albert

High Stimulus-Related Information in Barrel Cortex Inhibitory Interneurons

Vicente Reyes-Puerta, Suam Kim, Jyh-Jang Sun, Barbara Imbrosci, Werner Kilb, Heiko J. Luhmann

Emergence of Functional Specificity in Balanced Networks with Synaptic Plasticity

Sadra Sadeh, Claudia Clopath, Stefan Rotter

A Minimal Regulatory Network of Extrinsic and Intrinsic Factors Recovers Observed Patterns of CD4+ T Cell Differentiation and Plasticity

Mariana Esther Martinez-Sanchez, Luis Mendoza, Carlos Villarreal, Elena R. Alvarez-Buylla

Modeling the Impact of White-Plague Coral Disease in Climate Change Scenarios

Assaf Zvuloni, Yael Artzy-Randrup, Guy Katriel, Yossi Loya, Lewi Stone

Is Model Fitting Necessary for Model-Based fMRI?

Robert C. Wilson, Yael Niv

Deciphering Signaling Pathway Networks to Understand the Molecular Mechanisms of Metformin Action

Jingchun Sun, Min Zhao, Peilin Jia, Lily Wang, Yonghui Wu, Carissa Iverson, Yubo Zhou, Erica Bowton, Dan M. Roden, Joshua C. Denny, Melinda C. Aldrich, Hua Xu, Zhongming Zhao

Automated High-Throughput Characterization of Single Neurons by Means of Simplified Spiking Models

Christian Pozzorini, Skander Mensi, Olivier Hagens, Richard Naud, Christof Koch, Wulfram Gerstner

Revealing Pathway Dynamics in Heart Diseases by Analyzing Multiple Differential Networks

Xiaoke Ma, Long Gao, Georgios Karamanlidis, Peng Gao, Chi Fung Lee, Lorena Garcia-Menendez, Rong Tian, Kai Tan

Posterior Probability Matching and Human Perceptual Decision Making

Richard F. Murray, Khushbu Patel, Alan Yee

The Sense of Confidence during Probabilistic Learning: A Normative Account

Florent Meyniel, Daniel Schlunegger, Stanislas Dehaene

Stochastic Dynamics Underlying Cognitive Stability and Flexibility

Kai Ueltzhöffer, Diana J. N. Armbruster-Genç, Christian J. Fiebach

Behavioural Contagion Explains Group Cohesion in a Social Crustacean

Pierre Broly, Jean-Louis Deneubourg

The Physiological Molecular Shape of Spectrin: A Compact Supercoil Resembling a Chinese Finger Trap

Jeffrey W. Brown, Esther Bullitt, Sira Sriswasdi, Sandra Harper, David W. Speicher, C. James McKnight

Alternatively Spliced Homologous Exons Have Ancient Origins and Are Highly Expressed at the Protein Level

Federico Abascal, Iakes Ezkurdia, Juan Rodriguez-Rivas, Jose Manuel Rodriguez, Angela del Pozo, Jesús Vázquez, Alfonso Valencia, Michael L. Tress

Monte Carlo Planning Method Estimates Planning Horizons during Interactive Social Exchange

Andreas Hula, P. Read Montague, Peter Dayan

Particle Simulation of Oxidation Induced Band 3 Clustering in Human Erythrocytes

Hanae Shimo, Satya Nanda Vel Arjunan, Hiroaki Machiyama, Taiko Nishino, Makoto Suematsu, Hideaki Fujita, Masaru Tomita, Koichi Takahashi

Large-Scale Conformational Transitions and Dimerization Are Encoded in the Amino-Acid Sequences of Hsp70 Chaperones

Duccio Malinverni, Simone Marsili, Alessandro Barducci, Paolo De Los Rios

Energy Efficient Sparse Connectivity from Imbalanced Synaptic Plasticity Rules

João Sacramento, Andreas Wichert, Mark C. W. van Rossum

Measuring Fisher Information Accurately in Correlated Neural Populations

Ingmar Kanitscheider, Ruben Coen-Cagli, Adam Kohn, Alexandre Pouget

Related Articles

  1. Correction: Measuring Fisher Information Accurately in Correlated Neural Populations

Accurate Encoding and Decoding by Single Cells: Amplitude Versus Frequency Modulation

Gabriele Micali, Gerardo Aquino, David M. Richards, Robert G. Endres

Encoder-Decoder Optimization for Brain-Computer Interfaces

Josh Merel, Donald M. Pianto, John P. Cunningham, Liam Paninski

Differential Chromosome Conformations as Hallmarks of Cellular Identity Revealed by Mathematical Polymer Modeling

Imen Lassadi, Alain Kamgoué, Isabelle Goiffon, Nicolas Tanguy-le-Gac, Kerstin Bystricky

Detailed Per-residue Energetic Analysis Explains the Driving Force for Microtubule Disassembly

Ahmed T. Ayoub, Mariusz Klobukowski, Jack A. Tuszynski