2,141 results match your criteria Annual Review Of Biochemistry[Journal]


In Vitro Genetic Code Reprogramming for the Expansion of Usable Noncanonical Amino Acids.

Annu Rev Biochem 2022 06;91:221-243

Department of Chemistry, Graduate School of Science, The University of Tokyo, Tokyo, Japan; email:

Genetic code reprogramming has enabled us to ribosomally incorporate various nonproteinogenic amino acids (npAAs) into peptides in vitro. The repertoire of usable npAAs has been expanded to include not only l-α-amino acids with noncanonical sidechains but also those with noncanonical backbones. Despite successful single incorporation of npAAs, multiple and consecutive incorporations often suffer from low efficiency or are even unsuccessful. Read More

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The Life of SARS-CoV-2 Inside Cells: Replication-Transcription Complex Assembly and Function.

Annu Rev Biochem 2022 06;91:381-401

Ministry of Education Key Laboratory of Protein Science, School of Medicine, Tsinghua University, Beijing, China; email:

The persistence of the coronavirus disease 2019 (COVID-19) pandemic has resulted in increasingly disruptive impacts, and it has become the most devastating challenge to global health in a century. The rapid emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants challenges the currently available therapeutics for clinical application. Nonstructural proteins (also known as replicase proteins) with versatile biological functions play central roles in viral replication and transcription inside the host cells, and they are the most conserved target proteins among the SARS-CoV-2 variants. Read More

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Structural Mimicry in Microbial and Antimicrobial Amyloids.

Annu Rev Biochem 2022 06;91:403-422

Department of Biology, Technion-Israel Institute of Technology, Haifa, Israel; email:

The remarkable variety of microbial species of human pathogens and microbiomes generates significant quantities of secreted amyloids, which are structured protein fibrils that serve diverse functions related to virulence and interactions with the host. Human amyloids are associated largely with fatal neurodegenerative and systemic aggregation diseases, and current research has put forward the hypothesis that the interspecies amyloid interactome has physiological and pathological significance. Moreover, functional and molecular-level connections between antimicrobial activity and amyloid structures suggest a neuroimmune role for amyloids that are otherwise known to be pathological. Read More

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Validating Small Molecule Chemical Probes for Biological Discovery.

Annu Rev Biochem 2022 Jun 4;91:61-87. Epub 2022 Apr 4.

Structural Genomics Consortium, University of Toronto, Toronto, Ontario, Canada; email:

Small molecule chemical probes are valuable tools for interrogating protein biological functions and relevance as a therapeutic target. Rigorous validation of chemical probe parameters such as cellular potency and selectivity is critical to unequivocally linking biological and phenotypic data resulting from treatment with a chemical probe to the function of a specific target protein. A variety of modern technologies are available to evaluate cellular potency and selectivity, target engagement, and functional response biomarkers of chemical probe compounds. Read More

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Kinetic Proofreading.

Authors:
Hinrich Boeger

Annu Rev Biochem 2022 06 1;91:423-447. Epub 2022 Apr 1.

Department of Molecular, Cell and Developmental Biology, University of California, Santa Cruz, California; email:

Biochemistry and molecular biology rely on the recognition of structural complementarity between molecules. Molecular interactions must be both quickly reversible, i.e. Read More

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The Initiation of Eukaryotic DNA Replication.

Annu Rev Biochem 2022 06 23;91:107-131. Epub 2022 Mar 23.

Chromosome Replication Laboratory, The Francis Crick Institute, London, UK; email:

DNA replication in eukaryotic cells initiates from large numbers of sites called replication origins. Initiation of replication from these origins must be tightly controlled to ensure the entire genome is precisely duplicated in each cell cycle. This is accomplished through the regulation of the first two steps in replication: loading and activation of the replicative DNA helicase. Read More

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Driving E3 Ligase Substrate Specificity for Targeted Protein Degradation: Lessons from Nature and the Laboratory.

Annu Rev Biochem 2022 06 23;91:295-319. Epub 2022 Mar 23.

Centre for Targeted Protein Degradation, School of Life Sciences, University of Dundee, Dundee, United Kingdom; email:

Methods to direct the degradation of protein targets with proximity-inducing molecules that coopt the cellular degradation machinery are advancing in leaps and bounds, and diverse modalities are emerging. The most used and well-studied approach is to hijack E3 ligases of the ubiquitin-proteasome system. E3 ligases use specific molecular recognition to determine which proteins in the cell are ubiquitinated and degraded. Read More

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Structure and Mechanism of the Lipid Flippase MurJ.

Annu Rev Biochem 2022 06 23;91:705-729. Epub 2022 Mar 23.

Department of Biochemistry, Duke University Medical Center, Durham, North Carolina, USA; email:

Biosynthesis of many important polysaccharides (including peptidoglycan, lipopolysaccharide, and -linked glycans) necessitates the transport of lipid-linked oligosaccharides (LLO) across membranes from their cytosolic site of synthesis to their sites of utilization. Much of our current understanding of LLO transport comes from genetic, biochemical, and structural studies of the multidrug/oligosaccharidyl-lipid/polysaccharide (MOP) superfamily protein MurJ, which flips the peptidoglycan precursor lipid II. MurJ plays a pivotal role in bacterial cell wall synthesis and is an emerging antibiotic target. Read More

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Emerging Chemical Diversity and Potential Applications of Enzymes in the DMSO Reductase Superfamily.

Annu Rev Biochem 2022 06 23;91:475-504. Epub 2022 Mar 23.

Department of Chemistry and Chemical Biology, Harvard University, Cambridge, Massachusetts, USA; email:

Molybdenum- and tungsten-dependent proteins catalyze essential processes in living organisms and biogeochemical cycles. Among these enzymes, members of the dimethyl sulfoxide (DMSO) reductase superfamily are considered the most diverse, facilitating a wide range of chemical transformations that can be categorized as oxygen atom installation, removal, and transfer. Importantly, DMSO reductase enzymes provide high efficiency and excellent selectivity while operating under mild conditions without conventional oxidants such as oxygen or peroxides. Read More

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The Purinosome: A Case Study for a Mammalian Metabolon.

Annu Rev Biochem 2022 06 23;91:89-106. Epub 2022 Mar 23.

Department of Chemistry, The Pennsylvania State University, University Park, Pennsylvania, USA; email:

Over the past fifteen years, we have unveiled a new mechanism by which cells achieve greater efficiency in de novo purine biosynthesis. This mechanism relies on the compartmentalization of de novo purine biosynthetic enzymes into a dynamic complex called the purinosome. In this review, we highlight our current understanding of the purinosome with emphasis on its biophysical properties and function and on the cellular mechanisms that regulate its assembly. Read More

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Better, Faster, Cheaper: Recent Advances in Cryo-Electron Microscopy.

Annu Rev Biochem 2022 06 23;91:1-32. Epub 2022 Mar 23.

New York Structural Biology Center, New York, NY, USA; email:

Cryo-electron microscopy (cryo-EM) continues its remarkable growth as a method for visualizing biological objects, which has been driven by advances across the entire pipeline. Developments in both single-particle analysis and in situ tomography have enabled more structures to be imaged and determined to better resolutions, at faster speeds, and with more scientists having improved access. This review highlights recent advances at each stageof the cryo-EM pipeline and provides examples of how these techniques have been used to investigate real-world problems, including antibody development against the SARS-CoV-2 spike during the recent COVID-19 pandemic. Read More

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The Wnt Pathway: From Signaling Mechanisms to Synthetic Modulators.

Annu Rev Biochem 2022 06 18;91:571-598. Epub 2022 Mar 18.

Howard Hughes Medical Institute, Department of Developmental Biology, and Institute for Stem Cell Biology and Regenerative Medicine, School of Medicine, Stanford University, Stanford, California, USA; email:

The Wnt pathway is central to a host of developmental and disease-related processes. The remarkable conservation of this intercellular signaling cascade throughout metazoan lineages indicates that it coevolved with multicellularity to regulate the generation and spatial arrangement of distinct cell types. By regulating cell fate specification, mitotic activity, and cell polarity, Wnt signaling orchestrates development and tissue homeostasis, and its dysregulation is implicated in developmental defects, cancer, and degenerative disorders. Read More

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Metalloproteomics for Biomedical Research: Methodology and Applications.

Annu Rev Biochem 2022 06 18;91:449-473. Epub 2022 Mar 18.

Department of Chemistry and CAS-HKU Joint Laboratory of Metallomics on Health and Environment, University of Hong Kong, Hong Kong SAR, China; email:

Metals are essential components in life processes and participate in many important biological processes. Dysregulation of metal homeostasis is correlated with many diseases. Metals are also frequently incorporated into diagnosis and therapeutics. Read More

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Encapsulins.

Authors:
Tobias W Giessen

Annu Rev Biochem 2022 06 18;91:353-380. Epub 2022 Mar 18.

Departments of Biomedical Engineering and Biological Chemistry, University of Michigan Medical School, Ann Arbor, Michigan, USA; email:

Subcellular compartmentalization is a defining feature of all cells. In prokaryotes, compartmentalization is generally achieved via protein-based strategies. The two main classes of microbial protein compartments are bacterial microcompartments and encapsulin nanocompartments. Read More

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DNA-Protein Crosslinks and Their Resolution.

Annu Rev Biochem 2022 06 18;91:157-181. Epub 2022 Mar 18.

Department of Biochemistry, Ludwig Maximilians University, Munich, Germany; email:

Covalent DNA-protein crosslinks (DPCs) are pervasive DNA lesions that interfere with essential chromatin processes such as transcription or replication. This review strives to provide an overview of the sources and principles of cellular DPC formation. DPCs are caused by endogenous reactive metabolites and various chemotherapeutic agents. Read More

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Managing the Steady State Chromatin Landscape by Nucleosome Dynamics.

Annu Rev Biochem 2022 06 18;91:183-195. Epub 2022 Mar 18.

Department of Biochemistry and Molecular Genetics and RNA Bioscience Initiative, University of Colorado School of Medicine, Aurora, Colorado, USA.

Gene regulation arises out of dynamic competition between nucleosomes, transcription factors, and other chromatin proteins for the opportunity to bind genomic DNA. The timescales of nucleosome assembly and binding of factors to DNA determine the outcomes of this competition at any given locus. Here, we review how these properties of chromatin proteins and the interplay between the dynamics of different factors are critical for gene regulation. Read More

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The Role of DEAD-Box ATPases in Gene Expression and the Regulation of RNA-Protein Condensates.

Annu Rev Biochem 2022 06 18;91:197-219. Epub 2022 Mar 18.

Biozentrum, University of Basel, Basel, Switzerland; email:

DEAD-box ATPases constitute a very large protein family present in all cells, often in great abundance. From bacteria to humans, they play critical roles in many aspects of RNA metabolism, and due to their widespread importance in RNA biology, they have been characterized in great detail at both the structural and biochemical levels. DEAD-box proteins function as RNA-dependent ATPases that can unwind short duplexes of RNA, remodel ribonucleoprotein (RNP) complexes, or act as clamps to promote RNP assembly. Read More

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MAPK-Activated Protein Kinases: Servant or Partner?

Annu Rev Biochem 2022 06 18;91:505-540. Epub 2022 Mar 18.

Institute of Cell Biochemistry, Hannover Medical School, Hannover, Germany; email:

Mitogen-activated protein kinase (MAPK)-activated protein kinases (MAPKAPKs) are defined by their exclusive activation by MAPKs. They can be activated by classical and atypical MAPKs that have been stimulated by mitogens and various stresses. Genetic deletions of MAPKAPKs and availability of highly specific small-molecule inhibitors have continuously increased our functional understanding of these kinases. Read More

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Lipoproteins in the Central Nervous System: From Biology to Pathobiology.

Annu Rev Biochem 2022 06 18;91:731-759. Epub 2022 Mar 18.

Department of Neuroscience, Mayo Clinic, Jacksonville, Florida, USA; email:

The brain, as one of the most lipid-rich organs, heavily relies on lipid transport and distribution to maintain homeostasis and neuronal function. Lipid transport mediated by lipoprotein particles, which are complex structures composed of apolipoproteins and lipids, has been thoroughly characterized in the periphery. Although lipoproteins in the central nervous system (CNS) were reported over half a century ago, the identification of as the strongest genetic risk factor for Alzheimer's disease has accelerated investigation of the biology and pathobiology of lipoproteins in the CNS. Read More

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Macrocyclization and Backbone Modification in RiPP Biosynthesis.

Annu Rev Biochem 2022 06 18;91:269-294. Epub 2022 Mar 18.

Department of Chemistry and the Howard Hughes Medical Institute, University of Illinois at Urbana-Champaign, Urbana, Illinois, USA; email:

The past decade has seen impressive advances in understanding the biosynthesis of ribosomally synthesized and posttranslationally modified peptides (RiPPs). One of the most common modifications found in these natural products is macrocyclization, a strategy also used by medicinal chemists to improve metabolic stability and target affinity and specificity. Another tool of the peptide chemist, modification of the amides in a peptide backbone, has also been observed in RiPPs. Read More

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Influence of Nonspecific Interactions on Protein Associations: Implications for Biochemistry In Vivo.

Annu Rev Biochem 2022 06 14;91:321-351. Epub 2022 Mar 14.

Laboratory of Biochemistry and Genetics, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland, USA; email:

The cellular interior is composed of a variety of microenvironments defined by distinct local compositions and composition-dependent intermolecular interactions. We review the various types of nonspecific interactions between proteins and between proteins and other macromolecules and supramolecular structures that influence the state of association and functional properties of a given protein existing within a particular microenvironment at a particular point in time. The present state of knowledge is summarized, and suggestions for fruitful directions of research are offered. Read More

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The Function, Structure, and Origins of the ER Membrane Protein Complex.

Annu Rev Biochem 2022 06 14;91:651-678. Epub 2022 Mar 14.

Medical Research Council Laboratory of Molecular Biology, Cambridge, United Kingdom; email:

The endoplasmic reticulum (ER) is the site of membrane protein insertion, folding, and assembly in eukaryotes. Over the past few years, a combination of genetic and biochemical studies have implicated an abundant factor termed the ER membrane protein complex (EMC) in several aspects of membrane protein biogenesis. This large nine-protein complex is built around a deeply conserved core formed by the EMC3-EMC6 subcomplex. Read More

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Biochemistry, Cell Biology, and Pathophysiology of the Innate Immune cGAS-cGAMP-STING Pathway.

Annu Rev Biochem 2022 06 14;91:599-628. Epub 2022 Mar 14.

Department of Biochemistry, Stanford University, Stanford, California, USA.

In the decade since the discovery of the innate immune cyclic GMP-AMP synthase (cGAS)-2'3'-cyclic GMP-AMP (cGAMP)-stimulator of interferon genes (STING) pathway, its proper activation and dysregulation have been rapidly implicated in many aspects of human disease. Understanding the biochemical, cellular, and regulatory mechanisms of this pathway is critical to developing therapeutic strategies that either harness it to boost defense or inhibit it to prevent unwanted inflammation. In this review, we first discuss how the second messenger cGAMP is synthesized by cGAS in response to double-stranded DNA and cGAMP's subsequent activation of cell-type-dependent STING signaling cascades with differential physiological consequences. Read More

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Sensory TRP Channels in Three Dimensions.

Annu Rev Biochem 2022 06 14;91:629-649. Epub 2022 Mar 14.

Department of Biochemistry and Biophysics, University of California, San Francisco, California, USA; email:

Transient receptor potential (TRP) ion channels are sophisticated signaling machines that detect a wide variety of environmental and physiological signals. Every cell in the body expresses one or more members of the extended TRP channel family, which consists of over 30 subtypes, each likely possessing distinct pharmacological, biophysical, and/or structural attributes. While the function of some TRP subtypes remains enigmatic, those involved in sensory signaling are perhaps best characterized and have served as models for understanding how these excitatory ion channels serve as polymodal signal integrators. Read More

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The Structural Dynamics of Translation.

Annu Rev Biochem 2022 06 14;91:245-267. Epub 2022 Mar 14.

RNA Therapeutics Institute, University of Massachusetts Chan Medical School, Worcester, Massachusetts, USA; email:

Accurate protein synthesis (translation) relies on translation factors that rectify ribosome fluctuations into a unidirectional process. Understanding this process requires structural characterization of the ribosome and translation-factor dynamics. In the 2000s, crystallographic studies determined high-resolution structures of ribosomes stalled with translation factors, providing a starting point for visualizing translation. Read More

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High-Resolution Single-Molecule Magnetic Tweezers.

Annu Rev Biochem 2022 06 14;91:33-59. Epub 2022 Mar 14.

School of Biological Sciences and Institute for Molecular Biology and Genetics, Seoul National University, Seoul, South Korea; email:

Single-molecule magnetic tweezers deliver magnetic force and torque to single target molecules, permitting the study of dynamic changes in biomolecular structures and their interactions. Because the magnetic tweezer setups can generate magnetic fields that vary slowly over tens of millimeters-far larger than the nanometer scale of the single molecule events being observed-this technique can maintain essentially constant force levels during biochemical experiments while generating a biologically meaningful force on the order of 1-100 pN. When using bead-tether constructs to pull on single molecules, smaller magnetic beads and shorter submicrometer tethers improve dynamic response times and measurement precision. Read More

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Role of the TOM Complex in Protein Import into Mitochondria: Structural Views.

Annu Rev Biochem 2022 06 14;91:679-703. Epub 2022 Mar 14.

Faculty of Life Sciences, Kyoto Sangyo University, Kyoto, Japan; email:

Mitochondria are central to energy production, metabolism and signaling, and apoptosis. To make new mitochondria from preexisting mitochondria, the cell needs to import mitochondrial proteins from the cytosol into the mitochondria with the aid of translocators in the mitochondrial membranes. The translocase of the outer membrane (TOM) complex, an outer membrane translocator, functions as an entry gate for most mitochondrial proteins. Read More

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Ribonucleotide Incorporation by Eukaryotic B-Family Replicases and Its Implications for Genome Stability.

Annu Rev Biochem 2022 06 14;91:133-155. Epub 2022 Mar 14.

Genome Integrity and Structural Biology Laboratory, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina, USA; email:

Our current view of how DNA-based genomes are efficiently and accurately replicated continues to evolve as new details emerge on the presence of ribonucleotides in DNA. Ribonucleotides are incorporated during eukaryotic DNA replication at rates that make them the most common noncanonical nucleotide placed into the nuclear genome, they are efficiently repaired, and their removal impacts genome integrity. This review focuses on three aspects of this subject: the incorporation of ribonucleotides into the eukaryotic nuclear genome during replication by B-family DNA replicases, how these ribonucleotides are removed, and the consequences of their presence or removal for genome stability and disease. Read More

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Evolutionary Dynamics and Molecular Mechanisms of HORMA Domain Protein Signaling.

Annu Rev Biochem 2022 06 18;91:541-569. Epub 2022 Jan 18.

Department of Cellular & Molecular Medicine, University of California San Diego, La Jolla, California, USA; email:

Controlled assembly and disassembly of multi-protein complexes is central to cellular signaling. Proteins of the widespread and functionally diverse HORMA family nucleate assembly of signaling complexes by binding short peptide motifs through a distinctive safety-belt mechanism. HORMA proteins are now understood as key signaling proteins across kingdoms, serving as infection sensors in a bacterial immune system and playing central roles in eukaryotic cell cycle, genome stability, sexual reproduction, and cellular homeostasis pathways. Read More

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From Bioorganic Models to Cells.

Annu Rev Biochem 2021 06;90:57-76

Department of Chemistry, The Pennsylvania State University, University Park, Pennsylvania 16802, USA; email:

I endeavor to share how various choices-some deliberate, some unconscious-and the unmistakable influence of many others shaped my scientific pursuits. I am fascinated by how two long-term, major streams of my research, DNA replication and purine biosynthesis, have merged with unexpected interconnections. If I have imparted to many of the talented individuals who have passed through my lab a degree of my passion for uncloaking the mysteries hidden in scientific research and an understanding of the honesty and rigor it demands and its impact on the world community, then my mentorship has been successful. Read More

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