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Micronutrients
Published in Chuong Pham-Huy, Bruno Pham Huy, Food and Lifestyle in Health and Disease, 2022
Chuong Pham-Huy, Bruno Pham Huy
In general, an enzyme cannot function alone; it must be activated by one or many small molecules called coenzymes and cofactors. Some enzymes require several coenzymes and cofactors. Coenzymes and cofactors are small organic molecules or metal ions that are used by enzymes to help catalyze reactions (89–93). In other words, coenzymes are typically organic molecules that contain functionalities not found in proteins, while cofactors are catalytically essential molecules or ions that are covalently bound to enzymes (91). The term holoenzyme refers to an active enzyme complex: an enzyme combined with a coenzyme or a cofactor. An apoenzyme is an inactive enzyme: an enzyme without an activator (coenzyme or/and cofactor). The term prosthetic group is used to refer to minerals, activated vitamins, or other nonprotein compounds that are required for full enzyme activity (89–93). The prosthetic group remains bonded for the enzyme during the reaction. In some cases, the prosthetic group is covalently bound for its apoenzyme, while in other cases it is weakly bound to the active center by numerous weak interactions (93).
Transcriptionally Regulatory Sequences of Phylogenetic Significance
Published in S. K. Dutta, DNA Systematics, 2019
Escherichia coli is a natural host for bacteriophage. As has been amply documented, its RNA polymerase is larger and more complex than that of the phage, consisting of several subunits (α2, β, βʹ) totaling about 355,000 daltons.2 The precise recognition of promoters by this core polymerase requires an additional polypeptide, the sigma factor. Together, these polypeptide units constitute the polymerase holoenzyme.
Regulation of Synthesis of the β & β′ Subunits of RNA Polymerase of Escherichia Coli
Published in James F. Kane, Multifunctional Proteins: Catalytic/Structural and Regulatory, 2019
Rudolph Spangler, Geoffrey Zubay
Early attempts to purify the enzyme led to the isolation of a tetramer containing two α subunits, one β subunit, and one β′ subunit with molecular weights of 44,000, 150,000, and 165,000 dal tons, respectively. This enzyme was highly active in vitro when assayed with nicked template and a mixture of Mg2+ and Mn2+ divalent cations. Enzyme activity was greatly reduced when nicked template was replaced by intact DNA. High activity could be restored in the presence of the 70 kilodalton σ factor, which is now known to be required for correct promoter recognition. This factor dissociates shortly after initiation of transcription, so it is hardly surprising that it was lost in early purification procedures in which the assays for activity were not designed to score for correct initiation. Another small protein factor called co (not to be confused with the Type I topoisomerase of E. coli also called co) co-purifies with the so-called holoenzyme, but no functional activity has been demonstrated for this subunit. Other factors have been described which are believed to be required for the initiation or termination of transcription of certain gene products. The current description of the holoenzyme then is that of a pentamer containing σ, 2α, 1 β, and 1 β′ but not necessarily excluding other more or less firmly bound proteins which may be required in some or all transcriptional events.
Potential therapeutic targets for Mpox: the evidence to date
Published in Expert Opinion on Therapeutic Targets, 2023
Siddappa N Byrareddy, Kalicharan Sharma, Shrikesh Sachdev, Athreya S. Reddy, Arpan Acharya, Kaylee M. Klaustermeier, Christian L Lorson, Kamal Singh
VACV DNA genome replication is conducted by a holoenzyme consisting of multiple proteins [25]. An essential component of this holoenzyme is E9, the DNA-dependent DNA polymerase belonging to B family DNA polymerases. The MPXV genome encodes F8L (OPG71) [2], also a B family DNA-dependent DNA polymerase [27], which shares ~ 98% identity with VACV E9. The first B family DNA polymerase (RB69) structure showed an overall architecture of this class of enzymes [28]. This structure showed a canonical polymerase domain consisting of the Thumb, Palm, and Fingers subdomains, as seen in the structure of the Klenow Fragment (KF) of E. coli DNA polymerase I [29]. A notable difference between these polymerases is the relative position of the 3’ − 5’ exonuclease domain, which is ~ 180° opposite to that in KF relative to the polymerase active site. Subsequent crystal structures of the RB69 polymerase showed that residues of a β-hairpin positioned in the major groove of the template-primer played a role in the partitioning of primer to the 3’ − 5’ exonuclease site upon mismatch nucleotide incorporation [28,30–32]. Indeed, a resistance mutation on topologically similar β-hairpin in poxviruses’ DNA polymerase showed the relevance of the resistance mechanism of nucleotide analogs mediated by 3’ − 5’ exonuclease function (discussed below).
Function of protein kinase CK2 in thrombus formation
Published in Platelets, 2019
Emmanuel Ampofo, Beate M. Schmitt, Matthias W. Laschke, Michael D. Menger
CK2 is an evolutionary conserved and ubiquitously expressed serine/threonine kinase found in all eukaryotes [8]. The minimal consensus sequence for phosphorylation by this kinase is SXXE/D [8]. In contrast to other kinases, CK2 also accepts GTP as phosphoryl donor in place of ATP [9]. The CK2 holoenzyme consists of two catalytic CK2α and CK2α’ subunits as well as two regulatory CK2β subunits [10]. Accordingly, the tetrameric holoenzyme can be composed of α2β2, α’2β2 or αα’β2 [8]. Of interest, it has been demonstrated that solely the catalytic subunits are capable of phosphorylating various substrates. Based on this finding, Pinna [11] assigned the substrates of CK2 to three classes, depending on the composition of the subunits: (i) class-I substrates are phosphorylated by the catalytic subunits and the CK2 holoenzyme, (ii) class-II substrates are phosphorylated by CK2α as well as CK2α’ and (iii) class-III substrates are solely phosphorylated by the CK2 holoenzyme.
Structure-guided design of anti-cancer ribonucleotide reductase inhibitors
Published in Journal of Enzyme Inhibition and Medicinal Chemistry, 2019
Tessianna A. Misko, Yi-Ting Liu, Michael E. Harris, Nancy L. Oleinick, John Pink, Hsueh-Yun Lee, Chris G. Dealwis
Human ribonucleotide reductase (hRR) is a ubiquitous multi-subunit enzyme that is crucial for cell division and DNA repair1–4. RR catalyses the rate-determining step of dNTP synthesis by removing the 2′ hydroxyl of the ribose to generate a deoxyribose1. RR is critical for the maintenance of a balanced nucleotide pool in cells where imbalances lead to mutator phenotypes1,5,6. RR activity is maintained under tight regulation at the levels of transcription7, allostery1, cellular localisation8, and enzyme inhibition by Sml1 in Saccharomyces cerevisiae9. hRR is a multi-subunit enzyme consisting of a large subunit hRRM1, containing a catalytic site (C-site) and two allosteric sites known as the specificity site (S-site) and the activity site (A-site)1 (Figure 1). hRRM1 associates with the small subunit hRRM2 that houses a free radical essential for catalysis to form the holoenzyme10. ATP and dATP bind the A-site, inducing active and inactive hexamers, respectively11. Binding of dGTP, dTTP, dATP, or ATP to the S-site not only induces dimerisation of hRRM1 but also acts as a selection gate, regulating the relative Kcat/Km for the four NDP substrates: ADP, GDP, CDP, or UDP, respectively1.