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Human DOPA Decarboxylase: Catalysis and Involvement in Pharmacological Treatments for Parkinson’s Disease and Aromatic Amino Acid Decarboxylase Deficiency
Published in Peter Grunwald, Pharmaceutical Biocatalysis, 2020
Mariarita Bertoldi, Giada Rossignoli
A second important structural element is a mobile loop (Fig. 3.4) located at the dimeric interface and acting as a lid protruding from one subunit to the other and thus closing the neighboring active site during catalysis and correctly positioning key catalytic residues such as Tyr-332 that is responsible for an essential catalytic step (see below) (Bertoldi et al., 2002). This loop is invisible in the electron density map (Burkhard et al., 2001), thus suggesting that it is highly disordered, protease-sensitive and mobile and it has been modeled using the homologous enzymes histidine decarboxylase and glutamate decarboxylase (Fenalti et al., 2007; Komori et al., 2012; Paiardini et al., 2017). It is interesting to note that some loop residues from the neighboring subunit are considered important to positioning of the loop and to take part to the catalytic mechanism (Bertoldi et al., 2002; Fenalti et al., 2007; Komori et al., 2012).
Biocatalysis: An introduction
Published in Grunwald Peter, Biocatalysis and Nanotechnology, 2017
The next structural level of proteins is characterized by secondary structure elements, mainly the a-helix and the b-sheet. Their formation occurs spontaneously through the interaction between neighbored amino acid residues. These non-covalent interactions are stabilized by hydrogen bonds (binding energy ~40 kJ/mol) and fold into domains to yield a characteristic 3D or tertiary structure, maintained by forces acting between charged and/or hydrophobic amino acid residues, and dipole-dipole interactions. Different domains within a protein may be linked by oligopeptide loops. Another aspect contributing significantly to the stability of the protein molecule is the hydrophobic effect; it results from the fact that folding in an aqueous surrounding leads to a more or less water-free hydrophobic core whereas polar and charged amino acid residues are preferentially located on the protein surface. Finally, a variety of enzymes form a quaternary structure through the non-covalent interaction of subunits. The correct folding of proteins is assisted by ATP-dependent folding catalysts known as chaperones. They play, e.g., an important role in the endoplasmic reticulum and its associated degradation machinery in connection with the synthesis of glycoproteins (e.g., Ninagawa et al., 2014; Lederkremer, 2007).
Bacteriophage Scaffolds for Functional Assembly of Molecules and Nanomaterials
Published in Gilson Khang, Handbook of Intelligent Scaffolds for Tissue Engineering and Regenerative Medicine, 2017
Mi Hwa Oh, Jeong Heon Yu, Moon Young Yang, Yoon Sung Nam
Filamentous phages such as M13, fd, and f1 have been well studied for developing a phage display library.4,25 The M13 phage is a nonlytic phage, and its tail peptides, called pIII, are used to construct phage display libraries, which are commercially available as Ph.D.TM series from New England Biolabs, Inc. (NEB, Ipswich, MA, USA). The phage is approximately 6 nm in diameter and 930 nm in length and composed of a single-stranded circular DNA genome encapsulated by five different coat proteins(Fig. 26.2).4,24,25–26 The viral capsid components consist of major coat protein (pVIII) and minor coat proteins (pIII, pVI, pIX, and pVII). In the commercial pIII phage peptide libraries, the randomized peptide sequences of at least 2 billion different clones are expressed at the N-terminus of pIII. Each virion displays 5 copies of the peptide-pIII fusion coat protein linked via a short spacer sequence (Gly-Gly-Gly-Ser). Three different pIII libraries available from NEB are a 7-mer peptide library (Ph.D.-7), a 12-mer peptide library (Ph.D.-12), and a disulfide-constrained 7-mer peptide library (Ph.D.-C7C). The first residue of the inserted peptide is the first randomized position in both of the Ph.D.-7 and Ph.D.-12 libraries. In the Ph.D.-C7C library the inserted peptide has Ala-Cys at the N-terminus and forms a loop because the disulfide bond is formed between the two cysteine residues located at the both ends of an inserted sequence. The loop structure imposes conformational rigidity on the peptide and thus excludes many possible binding sequences. Exogenous peptides of up to about 30 amino acids can be displayed on the N terminus of minor coat protein pIII with 5–7 copies.4,24,26,27 The filamentous M13 phage has the diversity of 105–107 in phage-displayed peptide libraries. In the M13 phage system, the stop codon in the DNA genome has to be eliminated since the foreign peptide is fused to the N terminus of the coat protein4,24,26 In some cases, foreign peptides have been fused to the C terminus of coat protein pVI.28 However, the N terminus of coat protein pIII has been mostly used for displaying foreign peptides.4
Functional loop dynamics of the S-component of ECF transporter FolT
Published in Molecular Physics, 2018
Linqiong Qiu, Cong Shen, Jianing Song, Yingkai Zhang, John Z. H. Zhang
Loops often play important roles in the structures and functions of proteins. Thus, we discuss the dynamical functions of loops in FolT through analysis of Root Mean Square Deviation (RMSD) B-factor, DCCM and MI from three non-equilibrium and standard MD simulations.