Fascinating Proteins/Enzymes

A wonderful summary on the "Kinetics of Drug-Target Binding: A Guide for Drug Discovery" by Sam H***e in Comprehensive Pharmacology. Highly recommended for anybody wanting to appreciate the time evolution of small-molecule target interactions.

https://www.sciencedirect.com/science/article/pii/B9780128204726000116?via%3Dihub

Kinetics of Drug-Target Binding: A Guide for Drug Discovery The timing of activity of biological molecules has been quantified since the earliest studies on receptors and enzymes. Binding kinetics considers the…

An amazingly fluid and cogent summary on the visual interpretation of the Meaning of kcat/KM in Enzyme Kinetics by Chiwook Park from Purdue University

https://www.biorxiv.org/content/10.1101/2021.12.09.471995v1

Visual Interpretation of the Meaning of kcat/KM in Enzyme Kinetics k cat and k cat/ K M are the two fundamental kinetic parameters in enzyme kinetics. k cat is the first-order rate constant that determines the reaction rate when the enzyme is fully occupied at a saturating concentration of the substrate. k cat/ K M is the second-order rate constant that determines....

A Guide to Enzyme Kinetics in Early Drug discovery.

This guide discusses the application of enzyme kinetics in early drug discovery.

https://febs.onlinelibrary.wiley.com/doi/full/10.1111/febs.16404

FEBS Press Early drug discovery requires a balanced approach to structure–activity relationship (SAR)-guided medicinal chemistry employing both thermodynamic and kinetic parameters. This ‘guide to’ article intr...

Could a graph be any clearer as a flag bearer for use of kinetic information in drug discovery!!

In vivo Target Residence Time and Kinetic Selectivity: The Association Rate Constant as Determinant

https://doi.org/10.1016/j.tips.2016.06.008

A wonderful summary of "Enzymatic reactions inside biological condensates" from the Narlikar and Kutatelazde groups.

Which is the most important equation in biochemistry? This article, the first in a series of invited articles by FEBS Journal to popularize enzymology, discusses the Michaelis-Menten equation, its history, the assumptions that went into its derivation, its limitations and the journey beyond the steady state.
https://febs.onlinelibrary.wiley.com/doi/abs/10.1111/febs.16124

A classic with insightful information on the validity of Michaelis-Menten kinetics for intracellular systems

Cellular concentrations of enzymes and their substrates

https://www.sciencedirect.com/science/article/abs/pii/S0022519305802668

Cellular concentrations of enzymes and their substrates The activity of crude and pure enzyme preparations as well as the molecular weight of these enzymes were obtained from the literature for several orga…

Another classic on use of kinetic isotope effect (KIE) for probing catalysis by Amnon Kohen

Isotope Effects as Probes for Enzyme Catalyzed Hydrogen-Transfer Reactions

https://www.mdpi.com/1420-3049/18/5/5543

Isotope Effects as Probes for Enzyme Catalyzed Hydrogen-Transfer Reactions Kinetic Isotope effects (KIEs) have long served as a probe for the mechanisms of both enzymatic and solution reactions. Here, we discuss various models for the physical sources of KIEs, how experimentalists can use those models to interpret their data, and how the focus of traditional models has gro...

A classic by Judith Klinman, the pioneer of proton tunnelling in enzymes
The power of integrating kinetic isotope effects into the formalism of the Michaelis–Menten equation

https://febs.onlinelibrary.wiley.com/doi/full/10.1111/febs.12477

FEBS Press The integration of kinetic isotope effects into the formalism of the Michaelis-Menten equation began in the 1970s and has continued to this day. The impact of isotopic substitution on the primary ste...

https://www.sciencedirect.com/science/article/pii/S0079610704000240

Reaction kinetics in intracellular environments with macromolecular crowding: simulations and rate laws We review recent evidence illustrating the fundamental difference between cytoplasmic and test tube biochemical kinetics and thermodynamics, and showi…

Validity of the Michaelis–Menten equation – steady‐state or reactant stationary assumption: that is the question

https://febs.onlinelibrary.wiley.com/doi/full/10.1111/febs.12564

FEBS Press The Michaelis–Menten equation is generally used to estimate kinetic parameters when the steady‐state assumption is valid. This review shows that the Michaelis‐Menten equation can only lead to accurat...

https://pubs.acs.org/doi/10.1021/bi00892a002

Dithiothreitol, a New Protective Reagent for SH Groups* Download Hi-Res ImageDownload to MS-PowerPointCite This:Biochemistry 1964, 3, 4, 480-482 ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTDithiothreitol, a New Protective Reagent for SH Groups*W. W. ClelandCite this: Biochemistry 1964, 3, 4, 480–482Publication Date (Print):April 1, 1964Publication Hist...

https://science.sciencemag.org/content/236/4806/1252

Tinkering with enzymes: what are we learning? It is now possible, by site-directed mutagenesis of the gene, to change any amino acid residue in a protein to any other. In enzymology, application of this technique is leading to exciting new insights both into the mechanism of catalysis by particular enzymes, and into the basis of catalysis itsel...

https://pubs.acs.org/doi/10.1021/bi00670a032

Evolution of enzyme function and the development of catalytic efficiency Download Hi-Res ImageDownload to MS-PowerPointCite This:Biochemistry 1976, 15, 25, 5631-5640 ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTEvolution of enzyme function and the development of catalytic efficiencyW. John Albery and Jeremy R. KnowlesCite this: Biochemistry 1976, 15, 25, 5631–5640Publ...

FEBS Press This Words of Advice article frames the argument that enzymology is a rich discipline within the respective disciplines of mathematics, physics/chemistry and biology. It goes on to emphasize the nece...

A classic from the lab of Martin Karplus with Ron Elber

A method for determining reaction paths in large molecules: Application to myoglobin

https://www.sciencedirect.com/science/article/pii/0009261487805766

A method for determining reaction paths in large molecules: Application to myoglobin An algorithm is described for determining reaction paths between two known structures with many degrees of freedom. The method uses first-derivative t…

A novel high-throughput FLIPR Tetra based method for capturing highly confluent kinetic data for structure-kinetic relationship guided early drug discovery

https://chemrxiv.org/articles/preprint/A_Novel_High-Throughput_FLIPR_Tetra_Based_Method_for_Capturing_Highly_Confluent_Kinetic_Data_for_Structure-Kinetic_Relationship_Guided_Early_Drug_Discovery/13347524

A classic by Arieh Warshel
https://pubs.acs.org/doi/full/10.1021/cr0503106

Electrostatic Basis for Enzyme Catalysis Download Hi-Res ImageDownload to MS-PowerPointCite This:Chem. Rev. 2006, 106, 8, 3210-3235 ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTElectrostatic Basis for Enzyme CatalysisArieh Warshel, Pankaz K. Sharma, Mitsunori Kato, Yun Xiang, Hanbin Liu, and Mats H. M. OlssonView Author InformationDep...

A wonderful summary on rapid kinetic techniques

https://www.sciencedirect.com/science/article/pii/S0091679X07840155?via%3Dihub

Rapid Kinetic Techniques The elementary steps in complex biochemical reaction schemes (isomerization, dissociation, and association reactions) ultimately determine how fast an…

A fascinating reflection on the work in Gordon G Hammes's group at Duke University
https://www.jbc.org/content/early/2008/05/13/jbc.X800005200.full.pdf

www.jbc.org

https://www.nature.com/articles/d41586-020-03348-4

‘It will change everything’: DeepMind’s AI makes gigantic leap in solving protein structures Google’s deep-learning program for determining the 3D shapes of proteins stands to transform biology, say scientists.

An exceptional website by Antonio Baici discussing the kinetic mechanism of enzyme regulation
https://www.enzyme-modifier.ch/

Kinetic Mechanisms of Enzyme Inhibition and Activation – Easy tutorials, many examples, mechanism validation and advice for impeccable publishing Introduction Are there still people who believe that enzyme kinetics is a knotty discipline? This website, dedicated to the kinetics of enzyme-modifier interactions, aims at loosing any remaining knots in the classification and analysis of inhibition and activation mechanisms. The term modifier....

The review on non-MM kinetics accepted in ChemMedChem.
https://chemistry-europe.onlinelibrary.wiley.com/doi/10.1002/cmdc.202000791

Explicit Treatment of Non Michaelis‐Menten and Atypical Kinetics in Early Drug Discovery Click or tap to learn more.

A tour-de-force in enzymology teaching by Daniel Purich

https://www.elsevier.com/books/enzyme-kinetics-catalysis-and-control/9780123809247

Enzyme Kinetics: Catalysis and Control - 1st Edition Book Display

Another exceptional perspective on the role and impact of molecular motions within the protein on the enzyme's catalytic properties by Stephen J. Benkovic and Sharon Hammes-Schiffer.
https://science.sciencemag.org/content/301/5637/1196.abstract

A Perspective on Enzyme Catalysis The seminal hypotheses proposed over the years for enzymatic catalysis are scrutinized. The historical record is explored from both biochemical and theoretical perspectives. Particular attention is given to the impact of molecular motions within the protein on the enzyme's catalytic properties. A ca...

A exceptional review by Hunter and Anderson on what is cooperativity
https://onlinelibrary.wiley.com/doi/10.1002/anie.200902490

What is Cooperativity? The lamprey holds the clue to the link between supramolecular self‐assembly and allosteric ligand binding. Chelate cooperativity in self‐assembled structures results in denaturation behavior that is ...

This is a landmark review article by Geoff Holdgate, Thomas Meek and Rachel Grimley discussing about how mechanistic biology is relevant and important in the drug discovery field.
https://www.nature.com/articles/nrd.2017.219

Mechanistic enzymology in drug discovery: a fresh perspective Understanding the role of enzymes in disease states and the implementation of strategies to modulate their activities for therapeutic benefit remains a key focus for drug discovery. Here, Holdgate and colleagues assess the benefits of conducting and applying high-quality mechanistic enzymology studi...

Fascinating Proteins/Enzymes updated their website address.

"In the post-genomic world, why are we interested in enzyme kinetics? Judging from the volume of papers published every year, the discipline is far from becoming obsolete. Rather, there is a growing interest spanning from theoretical aspects to practical applications, such as those of pharmacological relevance, with enzyme inhibition in pole position."
https://portlandpress.com/biochemist/article/28/2/36/1728/Enzyme-kinetics-the-velocity-of-reactions

Enzyme kinetics: the velocity of reactions In the post-genomic world, why are we interested in enzyme kinetics? Judging from the volume of papers published every year, the discipline is far from becoming obsolete. Rather, there is a growing interest spanning from theoretical aspects to practical applications, such as those of pharmacological...

https://arxiv.org/abs/1905.03005
This paper argues how Michaelis-Menten assumptions are always violated at the molecular level!!

Enzyme kinetics at the molecular level The celebrated Michaelis-Menten (MM) expression provides a fundamental relation between the rate of enzyme catalysis and substrate concentration. The validity of this classical expression is, however, restricted to macroscopic amounts of enzymes and substrates and, thus, to processes with negligible...

An exceptional account of rate acceleration by Wolfenden
https://pubs.acs.org/doi/10.1021/ar000058i

The Depth of Chemical Time and the Power of Enzymes as Catalysts

The Depth of Chemical Time and the Power of Enzymes as Catalysts The fastest known reactions include reactions catalyzed by enzymes, but the rate enhancements that enzymes produce had not been fully appreciated until recently. In the absence of enzymes, these same reactions are among the slowest that have ever been measured, some with half-times approaching the a...

A follow up of "why nature chose phosphate" by Arieh Warshel, another nobel laureate
https://www.cambridge.org/core/journals/quarterly-reviews-of-biophysics/article/why-nature-really-chose-phosphate/030269AA621E6EA0CADDC263E6977930

Why nature really chose phosphate | Quarterly Reviews of Biophysics | Cambridge Core Why nature really chose phosphate - Volume 46 Issue 1

A classic, published in 1987, by Westheimer
https://science.sciencemag.org/content/235/4793/1173.long

Why nature chose phosphates Phosphate esters and anhydrides dominate the living world but are seldom used as intermediates by organic chemists. Phosphoric acid is specially adapted for its role in nucleic acids because it can link two nucleotides and still ionize; the resulting negative charge serves both to stabilize the dies...

quo-Vadis enzymology
"Enzymology has been a vital link between chemistry and biology in the second half of the twentieth century. A range of emerging scientific challenges is presenting the field with exciting opportunities to continue thriving in the future."
https://www.nature.com/articles/nchembio.1844

Quo vadis, enzymology? Enzymology has been a vital link between chemistry and biology in the second half of the twentieth century. A range of emerging scientific challenges is presenting the field with exciting opportunities to continue thriving in the future.

Another work emphasizing why non-Michaelis Menten kinetics is relevant and why caution should be exercised in the widespread application of MM kinetics without rigor and without satisfying the boundary conditions.
https://journals.plos.org/ploscompbiol/article?id=10.1371/journal.pcbi.1008258

Misuse of the Michaelis–Menten rate law for protein interaction networks and its remedy For over a century, the Michaelis–Menten (MM) rate law has been used to describe the rates of enzyme-catalyzed reactions and gene expression. Despite the ubiquity of the MM rate law, it accurately captures the dynamics of underlying biochemical reactions only so long as it is applied under the rig...

"The University is saddened to announce that Professor Chris Abell, Pro-Vice-Chancellor for Research, Professor of Biological Chemistry and Todd-Hamied Fellow of Christ’s College, has died suddenly at the age of 62." A huge loss to the biophysical community.
https://www.cam.ac.uk/research/news/professor-chris-abell-frs-fmedsci-1957-2020

Professor Chris Abell FRS, FMedSci (1957 – 2020) The University is saddened to announce that Professor Chris Abell, Pro-Vice-Chancellor for Research, Professor of Biological Chemistry and Todd-Hamied Fellow

Everything we know and don´t know about centromere inheritance and CENP-A nucleosome stability is now wonderfully summarized and digested by Sreyoshi Mitra in her review in https://rupress.org/jcb/article-standard/219/10/e202005099/152089/Stable-inheritance-of-CENP-A-chromatin-Inner

Enzyme Kinetics by progress curve simulation: An approach distinct from traditional treatments by Ken Johnson
https://kintekcorp.com/book/kinetic-analysis-for-the-new-enzymology

Kinetic Analysis for the New Enzymology In Kinetic Analysis for the New Enzymology , Dr. Johnson brings 40 years of research and sets forth a new approach to teach the conceptual basis underlying kinetic analysis, going beyond the steady-state to directly observe reactions occurring at the active sites of enzymes. Using the full power of