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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 biochemistry, allosteric regulation is the regulation of an enzyme by binding an effector molecule at a site other than the enzyme's active site.
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.
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.
In biochemistry, a conformational change is a change in the shape of a macromolecule, often induced by environmental factors.
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Gregory A. Petsko is an American biochemist and member of the National Academy of Sciences, the National Academy of Medicine, the American Academy of Arts and Sciences, and the American Philosophical Society. He is currently Professor of Neurology at the Ann Romney Center for Neurologic Diseases at Harvard Medical School and Brigham and Women's Hospital. He formerly had an endowed professorship in Neurology and Neuroscience at Weill Cornell Medical College and is still an adjunct professor of Biomedical Engineering at Cornell University, and is also the Gyula and Katica Tauber Professor, Emeritus, in biochemistry and chemistry at Brandeis University. On October 24, 2023, in a ceremony in the East Room of the White House, President Joe Biden presented Gregory Petsko and eight others with the National Medal of Science, the highest honor the United States can bestow on a scientist and engineer.
Malate dehydrogenase, mitochondrial also known as malate dehydrogenase 2 is an enzyme that in humans is encoded by the MDH2 gene.
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.
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Ruth Nussinov is an Israeli-American biologist born in Rehovot who works as a Professor in the Department of Human Genetics, School of Medicine at Tel Aviv University and is the Senior Principal Scientist and Principal Investigator at the National Cancer Institute, National Institutes of Health. Nussinov is also the Editor in Chief of the Current Opinion in Structural Biology and formerly of the journal PLOS Computational Biology.
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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
- ↑ "Kern CV" (PDF). Archived (PDF) from the original on 2019-10-09.
- ↑ "Life Sciences Faculty - Dorothee Kern". www.bio.brandeis.edu. Retrieved 2018-03-25.
- 1 2 3 Curry, Andrew: "Big Dreams Come True", Science, 326:792
- ↑ Tong, Amber (July 16, 2020). "Relay reaps $400M IPO windfall after drawing the curtain on motion-based drug design pipeline". Endpoints News. Archived from the original on 2020-07-18. Retrieved 2021-09-17.
- 1 2 3 "Our Team". Relay Therapeutics. Retrieved 2021-09-14.
- ↑ "Dorothee Kern's path from basketball star to founder of billion-dollar biotech(s?); Five Prime Therapeutics hands the reins to Genentech vet". Endpoints News. April 17, 2020. Archived from the original on 2020-04-20. Retrieved 2021-09-17.
- 1 2 "Dorothee Kern". German Academy of Sciences Leopoldina. Retrieved 26 May 2021.
- ↑ "Leopoldina Mission Statement". Nationale Akademie der Wissenschaften Leopoldina. Retrieved 2021-11-21.
- 1 2 3 4 5 6 7 "Choreographing a Cancer Treatment". Brandeis Magazine. Retrieved 2021-11-26.
- 1 2 3 4 "Dorothee Kern | Brandeis University". www.brandeis.edu. Retrieved 2021-11-26.
- ↑ https://ucsdtritons.com/sports/womens-basketball/roster/nadja-kern/7107
- ↑ 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.
- ↑ Kern, D. (1997-01-03). "How Thiamin Diphosphate Is Activated in Enzymes". Science. 275 (5296): 67–70. doi:10.1126/science.275.5296.67. PMID 8974393. S2CID 42796172.
- ↑ Kern, Dorothee; Zuiderweg, Erik RP (2003). "The role of dynamics in allosteric regulation". Current Opinion in Structural Biology. 13 (6): 748–757. doi:10.1016/j.sbi.2003.10.008. PMID 14675554.
- ↑ "Who We Are". Relay Therapeutics. Retrieved 2021-11-26.
- ↑ Nguyen, Vy; Wilson, Christopher; Hoemberger, Marc; Stiller, John B.; Agafonov, Roman V.; Kutter, Steffen; English, Justin; Theobald, Douglas L.; Kern, Dorothee (2017-01-20). "Evolutionary drivers of thermoadaptation in enzyme catalysis". Science. 355 (6322): 289–294. Bibcode:2017Sci...355..289N. doi:10.1126/science.aah3717. ISSN 0036-8075. PMC 5649376 . PMID 28008087.
- ↑ "Team". MOMA Therapeutics. Retrieved 2021-11-26.
- ↑ "MOMA Therapeutics: Drugging the molecular machines that underlie human disease". MOMA Therapeutics. 2020-04-11. Retrieved 2021-11-26.
