Enzymes

Metalloenzymes have been detailed in The Enzymes since its inception over half a century ago. Here, I review selected metal-containing enzyme highlights from early chapters in this series and I describe advances made since those contributions. Three topics are emphasized: nickel-containing enzymes, Fe(II)/2-oxoglutarate-dependent oxygenases, and enzymes containing non-canonical iron-sulfur clusters.

Although recognized earlier as subcellular entities by microscopists, mitochondria have been the subject of functional studies since 1922, when their biochemical similarities with bacteria were first noted. In this overview I trace the history of research on mitochondria from that time up to the present day, focussing on the major milestones of the overlapping eras of mitochondrial biochemistry, genetics, pathology and cell biology, and its explosion into new areas in the past 25 years. Nowadays, mitochondria are considered to be fully integrated into cell physiology, rather than serving specific functions in isolation...

Since its publication in 1950, the series "The Enzymes" has been established as an important reference book for researchers and students in the field of enzymology, biochemistry and biophysics and medical research. A number of scientists have served as a series editor for the Enzymes. Topics covered range from characterizations of various enzymes, biochemical processes and medical applications. This chapter provides an overview of the history of The Enzymes.

Nucleotide excision repair (NER) is a major DNA repair pathway conserved from bacteria to humans. Various DNA helicases, a group of enzymes capable of separating DNA duplex into two strands through ATP binding and hydrolysis, are required by NER to unwind the DNA duplex around the lesion to create a repair bubble and for damage verification and removal. In prokaryotes, UvrB helicase is required for repair bubble formation and damage verification, while UvrD helicase is responsible for the removal of the excised damage containing single-strand (ss) DNA fragment...

Since the discovery of DNA as the genetic material, scientists have been investigating how the information contained in this biological polymer is transmitted from generation to generation. X-ray crystallography, and more recently, cryo-electron microscopy techniques have been instrumental in providing essential information about the structure, functions and interactions of the DNA and the protein machinery (replisome) responsible for its replication. In this chapter, we highlight several works that describe the structure and structure-function relationships of the core components of the prokaryotic and eukaryotic replisomes...

Proteins are the most structurally diverse cellular biomolecules that act as molecular machines driving essential activities of all living organisms. To be functional, most of the proteins need to fold into a specific three-dimensional structure, which on one hand should be stable enough to oppose disruptive conditions and on the other hand flexible enough to allow conformational dynamics necessary for their biological functions. This compromise between stability and dynamics makes proteins susceptible to stress-induced misfolding and aggregation...

Mitochondria are multifunctional organelles that play a central role in a wide range of life-sustaining tasks in eukaryotic cells, including adenosine triphosphate (ATP) production, calcium storage and coenzyme generation pathways such as iron-sulfur cluster biosynthesis. The wide range of mitochondrial functions is carried out by a diverse array of proteins comprising approximately 1500 proteins or polypeptides. Degradation of these proteins is mainly performed by four AAA+ proteases localized in mitochondria...

In late November 2019, Prof. Lina M. Obeid passed away from cancer, a disease she spent her life researching and studying its intricate molecular underpinnings. Along with her husband, Prof. Yusuf A. Hannun, Obeid laid down the foundations of sphingolipid biochemistry and oversaw its remarkable evolution over the years. Lipids are a class of macromolecules that are primarily associated with cellular architecture. In fact, lipids constitute the perimeter of the cell in such a way that without them, there cannot be cells...

We present a brief review of the mitochondrial respiratory chain with emphasis on complexes I, III and IV, which contribute to the generation of protonmotive force across the inner mitochondrial membrane, and drive the synthesis of ATP by the process called oxidative phosphorylation. The basic structural and functional details of these complexes are discussed. In addition, we briefly review the information on the so-called supercomplexes, aggregates of complexes I-IV, and summarize basic physiological aspects of cell respiration...

Discovery of the class of protein kinase now dubbed a mitogen (or messenger)-activated protein kinase (MAPK) is an illustrative example of how disparate lines of investigation can converge and reveal an enzyme family universally conserved among eukaryotes, from single-celled microbes to humans. Moreover, elucidation of the circuitry controlling MAPK function defined a now overarching principle in enzyme regulation-the concept of an activation cascade mediated by sequential phosphorylation events. Particularly ground-breaking for this field of exploration were the contributions of genetic approaches conducted using several model organisms, but especially the budding yeast Saccharomyces cerevisiae...

The last review on transient-state kinetic methods in The Enzymes was published three decades ago (Johnson, K.A., 1992. The Enzymes, XX, 1-61). In that review the foundations were laid out for the logic behind the design and interpretation of experiments. In the intervening years the instrumentation has improved mainly in providing better sample economy and shorter dead times. More significantly, in 1992 we were just introducing methods for fitting data based on numerical integration of rate equations, but the software was slow and difficult to use...

No abstract text is available yet for this article.

NPAC is a transcriptional co-activator widely associated with the H3K36me3 epigenetic marks present in the gene bodies. NPAC plays a fundamental role in RNA polymerase progression, and its depletion downregulates gene transcription. In this chapter, we review the current knowledge on the functional and structural features of this multi-domain protein. NPAC (also named GLYR1 or NP60) contains a PWWP motif, a chromatin binder and epigenetic reader that is proposed to weaken the DNA-histone contacts facilitating polymerase passage through the nucleosomes...

The Nucleosome Remodeling and Deacetylating Complex (NuRD) is ubiquitously expressed in all metazoans. It combines nucleosome remodeling and histone deacetylating activities to generate inaccessible chromatin structures and to repress gene transcription. NuRD is involved in the generation and maintenance of a wide variety of lineage-specific gene expression programs during differentiation and in differentiated cells. A close cooperation with a large number of lineage-specific transcription factors is key to allow NuRD to function in many distinct differentiation contexts...

Transcriptional regulation in eukaryotic cells involves the activity of multifarious DNA-binding transcription factors and recruited corepressor complexes. Together, these complexes interact with the core transcriptional machinery, chromatin, and nuclear environment to effect complex patterns of gene regulation. Much focus has been paid to the action of master regulatory switches that are key to developmental and environmental responses, as these genetic elements have important phenotypic effects. The regulation of widely-expressed metabolic control genes has been less well studied, particularly in cases in which physically-interacting repressors and corepressors have subtle influences on steady-state expression...

Post-translational modifications of histone proteins control the expression of genes. Metabolites from central and one-carbon metabolism act as donor moieties to modify histones and regulate gene expression. Thus, histone modification and gene regulation are connected to the metabolite status of the cell. Histone modifiers, such as the SIN3 complex, regulate genes involved in proliferation and metabolism. The SIN3 complex contains a histone deacetylase and a histone demethylase, which regulate the chromatin landscape and gene expression...

The desired outcome of cancer therapies is the eradication of disease. This can be achieved when therapy exposure leads to therapy-induced cancer cell death as the dominant outcome. Theoretically, a permanent therapy-induced growth arrest could also contribute to a complete response, which has the potential to lead to remission. However, preclinical models have shown that therapy-induced growth arrest is not always durable, as recovering cancer cell populations can contribute to the recurrence of cancer. Significant research efforts have been expended to develop strategies focusing on the prevention of recurrence...

Nucleosomes are intrinsically immobile, and thus, ATP-dependent chromatin remodeling factors are needed to alter nucleosomes to facilitate DNA-directed processes such as transcription. More generally, chromatin remodeling factors mediate chromatin dynamics, which encompasses nucleosome assembly, movement, and disruption as well as histone exchange. Here, I present selected thoughts and perspectives on the past, present, and future of these fascinating ATP-driven motor proteins.

No abstract text is available yet for this article.

Publication of the second edition of The Enzymes series was initiated in 1959 and eight volumes were published. This chapter describes volumes 4-8. All eight volumes were edited by Paul D. Boyer, Henry Lardy and Karl Myerback. Authors and chapter titles are listed.