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Escherichia coli
Published in Yoshikatsu Murooka, Tadayuki Imanaka, Recombinant Microbes for Industrial and Agricultural Applications, 2020
Hisashi Yasueda, Hiroshi Matsui
In E. coli, translation is initiated by Af-formylmethionine tRNA, so TV-formylmethionine (fMet) is the NH2-terminal amino acid residue of nascent polypeptide chains [122]. Generally, the N-formyl group is quickly removed by a deformylase [123], and the methionine (Met) residue is successively removed by methionine aminopeptidase (MAP). However, the extent of Met processing by MAP is strongly affected by the penultimate amino acid. Thus, when the side chain of the adjacent amino acid is bulky, hydrophobic, or positively charged (e.g., Lys, Arg, Leu, He, Asn, or Phe), the initiator Met cannot be cleaved. In contrast, when the side chain is small and uncharged (e.g., Ala, Gly, Pro, Ser, or Thr), Met is removed efficiently [124-127]. These conclusions were based, in part, on the qualitative sequence analysis of endogenous cytosolic proteins. Hirel et al. [128] and Dalb0ge et al. [129] systematically investigated the extent of NH2-terminal Met excision from a set of 20 protein species (methionyl-tRNA synthetase and NH2-terminal-extended hGH), differing only in the penultimate amino acid residue. Their results demonstrated that the extent of cleavage decreases in parallel with the increase of the maximal side-chain length or the radius of gyration of the amino acid in the penultimate position.
Protein Degradation Inducers SNIPERs and Protacs against Oncogenic Proteins
Published in Peter Grunwald, Pharmaceutical Biocatalysis, 2019
Norihito Shibata, Nobumichi Ohoka, Takayuki Hattori, Mikihiko Naito
Cullin RING E3 ubiquitin ligases (CRLs) are multi-subunit complexes that catalyze the transfer of ubiquitin to specific substrate proteins. The complex of cullin1 (CUL1), S-phase kinase associated protein 1 (SKP1), and mammalian F-box protein β-transducin repeat-containing protein (β-TRCP) is a CRL known as CRL1β-TRCP. The β-TRCP of CRL1β-TRCP binds to IκBα and promotes its ubiquitination and degradation (Yaron et al., 1998). A 10 amino acid phosphopeptide segment of IκBα is both necessary and sufficient to mediate its binding to CRL1β-TRCP and subsequent ubiquitination and degradation (Yaron et al., 1997; Yaron et al., 1998). Dr. Deshaies’ and Crews’ groups designed and synthesized a series of hybrid molecules named PROTACs consisting of the IκBα phosphopeptide and a ligand of target proteins such as methionine aminopeptidase 2 (Sakamoto et al., 2001), ERα, and AR (Sakamoto et al., 2003). Although the β-TRCP-recruiting PROTACs induce ubiquitination and degradation of target proteins in vitro, they have low activity in cells, presumably because of the poor cell permeability of the employed peptide. To overcome this problem, the IκBα phosphopeptide was replaced by a hydroxyproline-containing pentapeptide from hypoxia-inducible factor a (HIF-1a), which is recognized by von Hippel-Lindau (VHL). VHL is a substrate recognition component of an E3 ubiquitin ligase complex containing cullin 2 (CUL2), RING-box protein 1 (RBX1), elongin B (ELOB), and elongin C (ELOC). The CUL2-RBX1-ELOB-ELOC-VHL complex (known as CRL2VHL) directs the ubiquitylation and subsequent proteasomal degradation of HIF-1a under normoxic conditions. VHL-recruiting PROTACs, consisting of the HIF-1a pentapeptide and a ligand of ERα or AR, are cell permeable and induce significant degradation of ERα and AR at 12.5 and 50 μM, respectively (Rodriguez-Gonzalez et al., 2008).
A review on bio-functional models of catechol oxidase probed by less explored first row transition metals
Published in Journal of Coordination Chemistry, 2022
Rashmi Rekha Tripathy, Shuvendu Singha, Sohini Sarkar
Before the nineteenth-century cobalt was used as pigment and coloring agent. Cobalt blue, cobalt green and cobalt violet, made with some common inorganic salts of cobalt or mixture of cobalt and other metals, have been used as the artist’s pigments since the middle ages. In modern age, cobalt-based super alloys have found applications in prosthetics and electrochemistry [93,94]. Being a part of vitamin B12 cobalt takes an essential part in metabolism of animals. Nitrile hydratase, prolidase, glucose isomerase, methylmalonyl-CoA carboxytransferase, aldehyde decarbonylase, lysine-2,3-aminomutase, bromoperoxidase and methionine aminopeptidase are examples of cobalt-containing enzymes that are present in various living systems. Recently, some of the cobalt(III) complexes have been found capable of antiviral and antimicrobial activities [95]. Apart from all biological and electrochemical applications, cobalt compounds are quite popular as oxidation catalysts. It can mimic catechol oxidase and act as effective bio-catalysts in catechol oxidation. Just like iron and manganese, varying oxidation states of cobalt (+2 and +3) can catalyze the oxidation with varying mechanisms. Metal centric path [7] and/or ligand centric radical path [41, 54, 68] may be followed during the catalytic cycle.