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Enzymes are proteins that act as biological catalysts by accelerating chemical reactions. The molecules upon which enzymes may act are called substrates, and the enzyme converts the substrates into different molecules known as products. Almost all metabolic processes in the cell need enzyme catalysis in order to occur at rates fast enough to sustain life. Metabolic pathways depend upon enzymes to catalyze individual steps. The study of enzymes is called enzymology and the field of pseudoenzyme analysis recognizes that during evolution, some enzymes have lost the ability to carry out biological catalysis, which is often reflected in their amino acid sequences and unusual 'pseudocatalytic' properties.
In the fields of biochemistry and pharmacology an allosteric regulator is a substance that binds to a site on an enzyme or receptor distinct from the active site, resulting in a conformational change that alters the protein's activity, either enhancing or inhibiting its function. In contrast, substances that bind directly to an enzyme's active site or the binding site of the endogenous ligand of a receptor are called orthosteric regulators or modulators.
Susan Lee Lindquist, ForMemRS was an American professor of biology at MIT specializing in molecular biology, particularly the protein folding problem within a family of molecules known as heat-shock proteins, and prions. Lindquist was a member and former director of the Whitehead Institute and was awarded the National Medal of Science in 2010.
In biology and biochemistry, the active site is the region of an enzyme where substrate molecules bind and undergo a chemical reaction. The active site consists of amino acid residues that form temporary bonds with the substrate, the binding site, and residues that catalyse a reaction of that substrate, the catalytic site. Although the active site occupies only ~10–20% of the volume of an enzyme, it is the most important part as it directly catalyzes the chemical reaction. It usually consists of three to four amino acids, while other amino acids within the protein are required to maintain the tertiary structure of the enzymes.
Aspartate carbamoyltransferase catalyzes the first step in the pyrimidine biosynthetic pathway.
Pyruvate kinase is the enzyme involved in the last step of glycolysis. It catalyzes the transfer of a phosphate group from phosphoenolpyruvate (PEP) to adenosine diphosphate (ADP), yielding one molecule of pyruvate and one molecule of ATP. Pyruvate kinase was inappropriately named before it was recognized that it did not directly catalyze phosphorylation of pyruvate, which does not occur under physiological conditions. Pyruvate kinase is present in four distinct, tissue-specific isozymes in animals, each consisting of particular kinetic properties necessary to accommodate the variations in metabolic requirements of diverse tissues.
In biochemistry and molecular biology, a binding site is a region on a macromolecule such as a protein that binds to another molecule with specificity. The binding partner of the macromolecule is often referred to as a ligand. Ligands may include other proteins, enzyme substrates, second messengers, hormones, or allosteric modulators. The binding event is often, but not always, accompanied by a conformational change that alters the protein's function. Binding to protein binding sites is most often reversible, but can also be covalent reversible or irreversible.
In biochemistry, a phosphatase is an enzyme that uses water to cleave a phosphoric acid monoester into a phosphate ion and an alcohol. Because a phosphatase enzyme catalyzes the hydrolysis of its substrate, it is a subcategory of hydrolases. Phosphatase enzymes are essential to many biological functions, because phosphorylation and dephosphorylation serve diverse roles in cellular regulation and signaling. Whereas phosphatases remove phosphate groups from molecules, kinases catalyze the transfer of phosphate groups to molecules from ATP. Together, kinases and phosphatases direct a form of post-translational modification that is essential to the cell's regulatory network.
A catalytic triad is a set of three coordinated amino acids that can be found in the active site of some enzymes. Catalytic triads are most commonly found in hydrolase and transferase enzymes. An acid-base-nucleophile triad is a common motif for generating a nucleophilic residue for covalent catalysis. The residues form a charge-relay network to polarise and activate the nucleophile, which attacks the substrate, forming a covalent intermediate which is then hydrolysed to release the product and regenerate free enzyme. The nucleophile is most commonly a serine or cysteine amino acid, but occasionally threonine or even selenocysteine. The 3D structure of the enzyme brings together the triad residues in a precise orientation, even though they may be far apart in the sequence.
Enzyme kinetics is the study of the rates of enzyme-catalysed chemical reactions. In enzyme kinetics, the reaction rate is measured and the effects of varying the conditions of the reaction are investigated. Studying an enzyme's kinetics in this way can reveal the catalytic mechanism of this enzyme, its role in metabolism, how its activity is controlled, and how a drug or a modifier might affect the rate.
In biochemistry, a conformational change is a change in the shape of a macromolecule, often induced by environmental factors.
Allosteric enzymes are enzymes that change their conformational ensemble upon binding of an effector which results in an apparent change in binding affinity at a different ligand binding site. This "action at a distance" through binding of one ligand affecting the binding of another at a distinctly different site, is the essence of the allosteric concept. Allostery plays a crucial role in many fundamental biological processes, including but not limited to cell signaling and the regulation of metabolism. Allosteric enzymes need not be oligomers as previously thought, and in fact many systems have demonstrated allostery within single enzymes. In biochemistry, allosteric regulation is the regulation of a protein by binding an effector molecule at a site other than the enzyme's active site.
Enzyme catalysis is the increase in the rate of a process by an "enzyme", a biological molecule. Most enzymes are proteins, and most such processes are chemical reactions. Within the enzyme, generally catalysis occurs at a localized site, called the active site.
Acetylcholinesterase (HGNC symbol ACHE; EC 3.1.1.7; systematic name acetylcholine acetylhydrolase), also known as AChE, AChase or acetylhydrolase, is the primary cholinesterase in the body. It is an enzyme that catalyzes the breakdown of acetylcholine and some other choline esters that function as neurotransmitters:
In molecular biology, proteins are generally thought to adopt unique structures determined by their amino acid sequences. However, proteins are not strictly static objects, but rather populate ensembles of conformations. Transitions between these states occur on a variety of length scales and time scales , and have been linked to functionally relevant phenomena such as allosteric signaling and enzyme catalysis.
Stephen James Benkovic is an American chemist known for his contributions to the field of enzymology. He holds the Evan Pugh University Professorship and Eberly Chair in Chemistry at The Pennsylvania State University. He has developed boron compounds that are active pharmacophores against a variety of diseases. Benkovic has concentrated on the assembly and kinetic attributes of the enzymatic machinery that performs DNA replication, DNA repair, and purine biosynthesis.
Lorena Beese is a James B. Duke Professor of Biochemistry and Duke Cancer Institute Member. Her research involves structural mechanisms underlying DNA replication and repair, neurodegenerative diseases, cancer, and microbial pathogenesis; X-ray crystallography and cryo-electron microscopy; structure-based drug design; protein-protein and protein-nucleic acid interactions, enzyme mechanisms, chemical biology, protein structure and function.
Katja Becker is a German physician and biochemist who has been serving as the president of the German Research Foundation (DFG) since 2020. She had previously been the organization's vice president from 2014 to 2019.
Pseudoenzymes are variants of enzymes that are catalytically-deficient, meaning that they perform little or no enzyme catalysis. They are believed to be represented in all major enzyme families in the kingdoms of life, where they have important signaling and metabolic functions, many of which are only now coming to light. Pseudoenzymes are becoming increasingly important to analyse, especially as the bioinformatic analysis of genomes reveals their ubiquity. Their important regulatory and sometimes disease-associated functions in metabolic and signalling pathways are also shedding new light on the non-catalytic functions of active enzymes, of moonlighting proteins, the re-purposing of proteins in distinct cellular roles. They are also suggesting new ways to target and interpret cellular signalling mechanisms using small molecules and drugs. The most intensively analyzed, and certainly the best understood pseudoenzymes in terms of cellular signalling functions are probably the pseudokinases, the pseudoproteases and the pseudophosphatases. Recently, the pseudo-deubiquitylases have also begun to gain prominence.
Edith Wilson Miles is a biochemist known for her work on the structure and function of enzymes, especially her work on tryptophan synthase.
References
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- ↑ Eisenmesser, Elan Zohar; Bosco, Daryl A.; Akke, Mikael; Kern, Dorothee (2002). "Enzyme Dynamics during Catalysis". Science. 295 (5559): 1520–1523. Bibcode:2002Sci...295.1520E. doi:10.1126/science.1066176. JSTOR 3076038. PMID 11859194. S2CID 28841021.
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