IUBMB Journal Highlights | April 2023

We are excited to highlight new research from the IUBMB Journals: IUBMB Life, BioFactors, Biotechnology and Applied Biochemistry, and Biochemistry and Molecular Biology Education.

Please also consider submitting your own research to the IUBMB Journals. You can expect to work with distinguished Editorial Board members and benefit from worldwide circulation and readership through our publishing partnership with Wiley. For more information about the journal and submissions, feel free to peruse the IUBMB journals website.

For now, please enjoy highlights of our recent content. Happy reading!



Special Issue: Volume 75, Issue 4IUBMB Vol 75 No 4

Issue Highlights

Edmond Fischer’s kinase legacy: History of the protein kinase inhibitor and protein kinase A

Susan S. Taylor, Friedrich W Herberg, Gianluigi Veglia, Jian Wu

First published: 28 February 2023

Although Fischer’s extraordinary career came to focus mostly on the protein phosphatases, after his co-discovery of Phosphorylase Kinase with Ed Krebs he was clearly intrigued not only by cAMP-dependent protein kinase (PKA), but also by the heat-stable, high-affinity protein kinase inhibitor (PKI). PKI is an intrinsically disordered protein that contains at its N-terminus a pseudo-substrate motif that binds synergistically and with high-affinity to the PKA catalytic (C) subunit. The sequencing and characterization of this inhibitor peptide (IP20) were validated by the structure of the PKA C-subunit solved first as a binary complex with IP20 and then as a ternary complex with ATP and two magnesium ions. A second motif, nuclear export signal (NES), was later discovered in PKI. Both motifs correspond to amphipathic helices that convey high-affinity binding. The dynamic features of full-length PKI, recently captured by NMR, confirmed that the IP20 motif becomes dynamically and sequentially ordered only in the presence of the C-subunit. The type I PKA regulatory (R) subunits also contain a pseudo-substrate ATPMg2-dependent high-affinity inhibitor sequence. PKI and PKA, especially the Cβ subunit, are highly expressed in the brain, and PKI expression is also cell cycle-dependent. In addition, PKI is now linked to several cancers. The full biological importance of PKI and PKA signaling in the brain, and their importance in cancer thus remains to be elucidated.

Kinetochore-catalyzed MCC formation: A structural perspective

Elyse S. Fischer

First published: 14 December 2022

The spindle assembly checkpoint (SAC) is a cellular surveillance mechanism that functions to ensure accurate chromosome segregation during mitosis. Macromolecular complexes known as kinetochores, act as the interface of sister chromatid attachment to spindle microtubules. In response to unattached kinetochores, the SAC activates its effector, the mitotic checkpoint complex (MCC), which delays mitotic exit until all sister chromatid pairs have achieved successful attachment to the bipolar mitotic spindle. Formation of the MCC (composed of Mad2, BubR1, Bub3 and Cdc20) is regulated by an Mps1 kinase-dependent phosphorylation signaling cascade which assembles and repositions components of the MCC onto a catalytic scaffold. This scaffold functions to catalyze the conversion of the HORMA-domain protein Mad2 from an “inactive” open-state (O-Mad2) into an “active” closed-Mad2 (C-Mad2), and simultaneous Cdc20 binding. Here, our current understanding of the molecular mechanisms underlying the kinetic barrier to C-Mad2:Cdc20 formation will be reviewed. Recent progress in elucidating the precise molecular choreography orchestrated by the catalytic scaffold to rapidly assemble the MCC will be examined, and unresolved questions will be highlighted. Ultimately, understanding how the SAC rapidly activates the checkpoint not only provides insights into how cells maintain genomic integrity during mitosis, but also provides a paradigm for how cells can utilize molecular switches, including other HORMA domain-containing proteins, to make rapid changes to a cell’s physiological state.




New Issue: Volume 49, Issue 2BioFactors cover

Issue Highlights

Astrocytic aerobic glycolysis provides lactate to support neuronal oxidative metabolism in the hippocampus

Cândida Dias, Eliana Fernandes, Rui M. Barbosa, João Laranjinha, Ana Ledo

First published: 17 April 2023

Under physiological conditions, the energetic demand of the brain is met by glucose oxidation. However, ample evidence suggests that lactate produced by astrocytes through aerobic glycolysis may also be an oxidative fuel, highlighting the metabolic compartmentalization between neural cells. Herein, we investigate the roles of glucose and lactate in oxidative metabolism in hippocampal slices, a model that preserves neuron–glia interactions. To this purpose, we used high-resolution respirometry to measure oxygen consumption (O2 flux) at the whole tissue level and amperometric lactate microbiosensors to evaluate the concentration dynamics of extracellular lactate. We found that lactate is produced from glucose and transported to the extracellular space by neural cells in hippocampal tissue. Under resting conditions, endogenous lactate was used by neurons to support oxidative metabolism, which was boosted by exogenously added lactate even in the presence of excess glucose. Depolarization of hippocampal tissue with high K+ significantly increased the rate of oxidative phosphorylation, which was accompanied by a transient decrease in extracellular lactate concentration. Both effects were reverted by inhibition of the neuronal lactate transporter, monocarboxylate transporters 2 (MCT2), supporting the concept of an inward flux of lactate to neurons to fuel oxidative metabolism. We conclude that astrocytes are the main source of extracellular lactate which is used by neurons to fuel oxidative metabolism, both under resting and stimulated conditions.



Biotechnology and Applied Biochemistry

New Issue: Volume 70, Issue 2BAB cover

Issue Highlights

Reconnoitring the antioxidant and antibacterial potential of different fruits after tannin acyl hydrolase mediated biotransformation

Rippin, Anil K. Sharma, Vikas Beniwal

First published: 25 March 2023

Condensed and hydrolyzable tannins are secondary metabolites present in almost every plant part. Tannase enzyme acts on hydrolyzable tannins to produce gallic acid and tannase-mediated end-products with immense therapeutic potential. Seven different fruits with significant presence of hydrolyzable tannin content were selected to check for phenol, tannin, and hydrolyzable tannin contents. Prunus domestica had the maximum phenol content, that is, 85.4 ± 0.207, followed by Syzygium cumini, Fragaria ananassa, Rubus fruticosus, and Psidium guajava. Plum showed the maximum number of hydrolyzable tannins. Fruit extracts were subjected to tannase hydrolysis and their antimicrobial and antioxidant activities were determined. There was a significant increase in the antioxidant abilities of the fruits with Punica granatum extract, displaying the highest decline of 132 units of IC50 followed by F. ananassa hydrolyzable extract, showing a decrease from 224.75 to 119.98 μg/mL. The extracts also depicted a significant increase in antibacterial activity after hydrolysis against Escherichia coli, Pseudomonas aeruginosa, Bacillus subtilis, and Staphylococcus aureus with Rubus idaeus aqueous extract observed to be most effective against E. coli. The increase in antioxidant and antibacterial activity can be attributed to the production of tannase-mediated products formed after the biotransformation of hydrolyzable tannins present in the aqueous extracts.



Biochemistry and Molecular Biology Education

Biochemistry and Molecular Biology Education

New Issue: Volume 51, Issue 2

Issue Highlights

An idea to explore: Augmented reality and LEGO® brick modeling in the biochemistry and cell biology classroom-two tactile ways to teach biomolecular structure—Function

Swati Agrawal, Shane Austin

First published: 06 April 2023

We present here two accessible ways for enhanced understanding of complex biological structures and their function in undergraduate Biology and Biochemistry classrooms. These methods can be applied for in-class instruction as well as for remote lessons, as they are cheap, easily available and easy to implement. LEGO® bricks and MERGE CUBE based augmented reality can be applied to make three-dimensional representation for any structure available on PDB. We envisage these techniques to be useful for students when visualizing simple stereochemical problems or complex pathway interactions.



Did you know? Wiley and Jisc just signed an agreement that allows UK authors to publish Open Access in the IUBMB Journals at no cost to them.

Thanks to a partnership our publisher Wiley has signed with Jisc, certain UK institutions now have full access to journals published by Wiley, including the IUBMB Journals. Further, the partnership enables authors at participating UK institutions to publish open access at no cost to them in the IUBMB Journals. Payment of the associated Article Publication Charges (APC) would be covered via the partnership, and authors will not need to cover the APCs from their own pockets.

Wiley has also signed similar agreements with universities in Germany, the Netherlands, Austria, Norway, Hungary, Finland, Sweden, and with the US-based OhioLink And VIVA.

Submit your research to the IUBMB Journals today.


Molecular Aspects of Medicine

Molecular Aspects of Medicine cover

Volume 91 (June 2023) 101151
Protein structure-based in-silico approaches to drug discovery: Guide to COVID-19 therapeutics

by Yash Gupta a, Oleksandr V. Savytskyi b f, Matt Coban b d, Amoghavarsha Venugopal a, Vasili Pleqi a, Caleb A. Weber b, Rohit Chitale a e, Ravi Durvasula a, Christopher Hopkins f, Prakasha Kempaiah a, Thomas R. Caulfield b c g h i


Aspects of Molecular Medicine

Molecular Aspects of Medicine cover

Volume 1 (2023) 100008
sgRNAs: A SARS-CoV-2 emerging issue

by Antonio Mori Antonio Mori 1, Denise Lavezzari 1, Elena Pomari, Michela Deiana, Chiara Piubelli, Maria Rosaria Capobianchi, Concetta Castilletti


If you are interested in reviewing for Aspects of Molecular Medicine, or would like to apply to be an Editorial Board Member, visit our journal homepage to find out more.