scholarly journals A tangled tale of convergence and divergence: archaeal chromosomal proteins and Chromo-like domains in bacteria and eukaryotes

2017 ◽  
Author(s):  
Gurmeet Kaur ◽  
Lakshminarayan M. Iyer ◽  
Srikrishna Subramanian ◽  
L. Aravind
Keyword(s):  
Hydrophobic Interactions ◽  
Structural Similarity ◽  
Metal Chelation ◽  
Amino Groups ◽  
Chromosomal Proteins ◽  
Peptide Recognition ◽  
Eukaryotic Proteins ◽  
Aromatic Cage ◽  
Related Proteins ◽  
Zinc Ribbon

AbstractThe Chromo-like superfamily of SH3-fold β-barrel domains recognize epigenetic marks in eukaryotic proteins. Their provenance has been placed either in archaea, based on apparent structural similarity to chromatin-compacting Sul7d and Cren7 proteins, or in bacteria based on the presence of sequence homologs. Using sequence and structural evidence we establish that the archaeal Cren7/Sul7 proteins emerged from a zinc ribbon (ZnR) ancestor. Further, we show that the ancestral eukaryotic Chromo-like domains evolved from bacterial precursors acquired from early endosymbioses, which already possessed an aromatic cage for recognition of modified amino-groups. These bacterial versions are part of a radiation of secreted SH3-fold domains, which spawned both chromo-like domains and classical SH3 domains in the context of peptide-recognition in the peptidoglycan. This establishes that Cren7/Sul7 converged to a "SH3”-like state from a ZnR precursor via the loss of metal-chelation and acquisition of stronger hydrophobic interactions; it is unlikely to have participated in the evolution of the chromo-like domains. We show that archaea possess several Cren7/Sul7-related proteins with intact Zn-chelating ligands, which we predict to play previously unstudied roles in cell-division comparable to the PRC barrel.

scholarly journals Lysyl oxidase activity and elastin/glycosaminoglycan interactions in growing chick and rat aortas.

1987 ◽  
Vol 105 (3) ◽  
pp. 1463-1469 ◽  
Author(s):  
C Fornieri ◽  
M Baccarani-Contri ◽  
D Quaglino ◽  
I Pasquali-Ronchetti
Keyword(s):  
Hydrophobic Interactions ◽  
Isonicotinic Acid ◽  
Lysyl Oxidase ◽  
Acid Hydrazide ◽  
Elastic Fibers ◽  
Amino Groups ◽  
Lysine Residues ◽  
Oxidase Inhibition

Hydrophobic tropoelastin molecules aggregate in vitro in physiological conditions and form fibers very similar to natural ones (Bressan, G. M., I. Pasquali Ronchetti, C. Fornieri, F. Mattioli, I. Castellani, and D. Volpin, 1986, J. Ultrastruct. Molec. Struct. Res., 94:209-216). Similar hydrophobic interactions might be operative in in vivo fibrogenesis. Data are presented suggesting that matrix glycosaminoglycans (GAGs) prevent spontaneous tropoelastin aggregation in vivo, at least up to the deamination of lysine residues on tropoelastin by matrix lysyl oxidase. Lysyl oxidase inhibitors beta-aminopropionitrile, aminoacetonitrile, semicarbazide, and isonicotinic acid hydrazide were given to newborn chicks, to chick embryos, and to newborn rats, and the ultrastructural alterations of the aortic elastic fibers were analyzed and compared with the extent of the enzyme inhibition. When inhibition was greater than 65% all chemicals induced alterations of elastic fibers in the form of lateral aggregates of elastin, which were always permeated by cytochemically and immunologically recognizable GAGs. The number and size of the abnormal elastin/GAGs aggregates were proportional to the extent of lysyl oxidase inhibition. The phenomenon was independent of the animal species. All data suggest that, upon inhibition of lysyl oxidase, matrix GAGs remain among elastin molecules during fibrogenesis by binding to positively charged amino groups on elastin. Newly synthesized and secreted tropoelastin has the highest number of free epsilon amino groups, and, therefore, the highest capability of binding to GAGs. These polyanions, by virtue of their great hydration and dispersing power, could prevent random spontaneous aggregation of hydrophobic tropoelastin in the extracellular space.

Molecular evolution of the actin family

2002 ◽  
Vol 115 (13) ◽  
pp. 2619-2622 ◽  
Author(s):  
Holly V. Goodson ◽  
William F. Hawse
Keyword(s):  
Phylogenetic Analysis ◽  
Molecular Evolution ◽  
Chromatin Remodeling ◽  
The Core ◽  
Nuclear Process ◽  
Core Set ◽  
Eukaryotic Proteins ◽  
Related Proteins

Members of the actin family have well-characterized cytoskeletal functions,but actin and actin-related proteins (ARPs) have also been implicated in nuclear activities. Previous analyses of the actin family have identified four conserved subfamilies, but many actin-related proteins (ARPs) do not fall into these groups. A new systematic phylogenetic analysis reveals that at least eight ARP subfamilies are conserved from humans to yeast, indicating that these ARPs are part of the core set of eukaryotic proteins. Members of at least three subfamilies appear to be involved in chromatin remodeling,suggesting that ARPs play ancient, fundamental roles in this nuclear process.

scholarly journals Parameters for Irreversible Inactivation of Monoamine Oxidase

Molecules ◽  
2020 ◽  
Vol 25 (24) ◽  
pp. 5908
Author(s):  
Rona R. Ramsay ◽  
Livia Basile ◽  
Antonin Maniquet ◽  
Stefanie Hagenow ◽  
Matteo Pappalardo ◽  
...  
Keyword(s):  
Molecular Dynamics ◽  
Hydrophobic Interactions ◽  
Irreversible Inhibitor ◽  
Reversible Binding ◽  
Mao B ◽  
Irreversible Inhibitors ◽  
Aromatic Cage ◽  
Covalent Adduct ◽  
Mao A ◽  
New Compounds

The irreversible inhibitors of monoamine oxidases (MAO) slow neurotransmitter metabolism in depression and neurodegenerative diseases. After oxidation by MAO, hydrazines, cyclopropylamines and propargylamines form a covalent adduct with the flavin cofactor. To assist the design of new compounds to combat neurodegeneration, we have updated the kinetic parameters defining the interaction of these established drugs with human MAO-A and MAO-B and analyzed the required features. The Ki values for binding to MAO-A and molecular models show that selectivity is determined by the initial reversible binding. Common to all the irreversible inhibitor classes, the non-covalent 3D-chemical interactions depend on a H-bond donor and hydrophobic-aromatic features within 5.7 angstroms apart and an ionizable amine. Increasing hydrophobic interactions with the aromatic cage through aryl halogenation is important for stabilizing ligands in the binding site for transformation. Good and poor inactivators were investigated using visible spectroscopy and molecular dynamics. The initial binding, close and correctly oriented to the FAD, is important for the oxidation, specifically at the carbon adjacent to the propargyl group. The molecular dynamics study also provides evidence that retention of the allenyl imine product oriented towards FADH− influences the formation of the covalent adduct essential for effective inactivation of MAO.

scholarly journals Translocon-associated protein TRAP δ and a novel TRAP-like protein are coordinately expressed with pro-opiomelanocortin in Xenopus intermediate pituitary

1995 ◽  
Vol 312 (1) ◽  
pp. 205-213 ◽  
Author(s):  
J C M Holthuis ◽  
M C H M van Riel ◽  
G J M Martens
Keyword(s):  
Protein Complex ◽  
Transmembrane Protein ◽  
Structural Similarity ◽  
White Background ◽  
Secretory Proteins ◽  
Animal Kingdom ◽  
Alternatively Spliced ◽  
A Subunit ◽  
Polypeptide Chains ◽  
Related Proteins

In the intermediate pituitary gland of Xenopus laevis, the expression levels of the prohormone pro-opiomelanocortin (POMC) can be readily manipulated. When the animal is placed on a black background, the gene for POMC is actively transcribed, whereas on a white background the gene is virtually inactive. In this study, we characterized two genes whose transcript levels in the intermediate pituitary are regulated in coordination with that for POMC. One of these codes for a protein homologous to translocon-associated protein TRAP delta, a subunit of a transmembrane protein complex located at the site where nascent secretory proteins enter the endoplasmic reticulum (ER). Both Xenopus and mice were found to express an alternatively spliced transcript that gives rise to a previously unknown version of the TRAP delta protein. The product of the second gene is a novel and highly conserved protein with structural similarity to glycoprotein gp25L, a constituent of another translocon-associated protein complex. A database search revealed the existence of a novel family of gp25L-related proteins whose members occur throughout the animal kingdom. Together, our data imply that (i) the group of ER proteins surrounding translocating polypeptide chains may be far more complex than previously expected, and (ii) a number of the accessory components of the translocon participate in early steps of prohormone biosynthesis.

scholarly journals Crystal structure of theMSMEG_4306gene product fromMycobacterium smegmatis

2018 ◽  
Vol 74 (3) ◽  
pp. 166-173
Author(s):  
Adarsh Kumar ◽  
Subramanian Karthikeyan
Keyword(s):  
Crystal Structure ◽  
Coiled Coil ◽  
Structural Similarity ◽  
Data Bank ◽  
Zinc Ion ◽  
Terminal Region ◽  
Amino Acid Residues ◽  
Secretion Systems ◽  
C Terminus ◽  
Zinc Ribbon

TheMSMEG_4306gene fromMycobacterium smegmatisencodes a protein of unknown function with 242 amino-acid residues that contains a conserved zinc-ribbon domain at its C-terminus. Here, the crystal structure of MSMEG_4306 determined by the single-wavelength anomalous dispersion method using just one zinc ion co-purified with the protein is reported. The crystal structure of MSMEG_4306 shows a coiled-coil helix domain in the N-terminal region and a zinc-ribbon domain in the C-terminal region. A structural similarity search against the Protein Data Bank using MSMEG_4306 as a query revealed two similar structures, namely CT398 fromChlamydia trachomatisand HP0958 fromHelicobacter pylori, although they share only ∼15% sequence identity with MSMEG_4306. Based on comparative analysis, it is predicted that MSMEG_4306 may be involved in secretion systems, possibly by interacting with multiple proteins or nucleic acids.

scholarly journals MPDB: a unified multi-domain protein structure database integrating structural analogue detection

2021 ◽  
Author(s):  
Chunxiang Peng ◽  
Xiaogen Zhou ◽  
Yuhao Xia ◽  
Yang Zhang ◽  
Guijun Zhang
Keyword(s):  
Protein Structure ◽  
Structure Prediction ◽  
Protein Structures ◽  
Structural Similarity ◽  
Structure Database ◽  
Eukaryotic Proteins ◽  
Domain Models ◽  
Input Domain ◽  
Domain Protein ◽  
Multiple Domains

With the development of protein structure prediction methods and biological experimental determination techniques, the structure of single-domain proteins can be relatively easier to be modeled or experimentally solved. However, more than 80% of eukaryotic proteins and 67% of prokaryotic proteins contain multiple domains. Constructing a unified multi-domain protein structure database will promote the research of multi-domain proteins, especially in the modeling of multi-domain protein structures. In this work, we develop a unified multi-domain protein structure database (MPDB). Based on MPDB, we also develop a server with two functional modules: (1) the culling module, which filters the whole MPDB according to input criteria; (2) the detection module, which identifies structural analogues of the full-chain according to the structural similarity between input domain models and the protein in MPDB. The module can discover the potential analogue structures, which will contribute to high-quality multi-domain protein structure modeling.

Relation between penicillin and N -acetylmuramic acid in the binding site of lysozyme

1967 ◽  
Vol 167 (1009) ◽  
pp. 441-442 ◽  
Keyword(s):  
Binding Site ◽  
Hydrophobic Interactions ◽  
Structural Similarity ◽  
Side Chain ◽  
Phenoxymethyl Penicillin ◽  
Polar Groups ◽  
Ether Oxygen ◽  
Ring Nitrogen ◽  
Maximum Similarity ◽  
Enzyme Complexes

It has been known for some time that penicillin exerts its antibiotic action by inhibiting the synthesis of the cell wall mucopeptide polymer in sensitive bacteria. Richmond and I, seeking an explanation for this specificity, suggested that there was a structural similarity between penicillin and N -acetylmuramic acid, one of the components in the polymer, and that penicillin might inhibit one of the enzymes involved in the synthesis of the polymer because of this similarity (Collins & Richmond 1962). It is therefore very interesting to hear that phenoxymethyl-penicillin has a single binding site in the lysozyme molecule, which is also the binding site for α -benzyl- N -acetylmuramic acid (the site number 5, in Dr Phillips’s notation). With the data from the 6 Å resolution picture of these enzyme complexes obtained by Dr Johnson, it is not possible to determine which groups are involved in interactions between lysozyme and the bound molecules of penicillin and benzy- N -acetylmuramic acid. Examination of the lysozyme model in the region where these molecules are bound shows some groups which may be involved in hydrophobic interactions, but few polar groups. This weakens the possibility that the similarity suggested by Richmond and me underlies the interaction between the molecules in these complexes, since we found the maximum similarity to lie in the disposition of polar groups in penicillin and in N -acetylmuramic acid. Briefly, we drew an analogy between the carboxyl groups, between the ring nitrogen atom in penicillin and the ether oxygen atom in the lactyl side-chain of N -acetylmuramic acid, and between the carbonyl groups in the amide links in the two molecules.

scholarly journals A Novel Family of Soluble Minimal Scaffolds Provides Structural Insight into the Catalytic Domains of Integral Membrane Metallopeptidases

2013 ◽  
Vol 288 (29) ◽  
pp. 21279-21294 ◽  
Author(s):  
Mar López-Pelegrín ◽  
Núria Cerdà-Costa ◽  
Francisco Martínez-Jiménez ◽  
Anna Cintas-Pedrola ◽  
Albert Canals ◽  
...  
Keyword(s):  
Catalytic Domain ◽  
Structural Similarity ◽  
Rational Drug Design ◽  
Sequence Comparisons ◽  
Catalytic Domains ◽  
Rational Drug ◽  
Leukotriene A4 Hydrolase ◽  
Merops Database ◽  
Leukotriene A4 ◽  
Related Proteins

In the search for structural models of integral-membrane metallopeptidases (MPs), we discovered three related proteins from thermophilic prokaryotes, which we grouped into a novel family called “minigluzincins.” We determined the crystal structures of the zymogens of two of these (Pyrococcus abyssi proabylysin and Methanocaldococcus jannaschii projannalysin), which are soluble and, with ∼100 residues, constitute the shortest structurally characterized MPs to date. Despite relevant sequence and structural similarity, the structures revealed two unique mechanisms of latency maintenance through the C-terminal segments previously unseen in MPs as follows: intramolecular, through an extended tail, in proabylysin, and crosswise intermolecular, through a helix swap, in projannalysin. In addition, structural and sequence comparisons revealed large similarity with MPs of the gluzincin tribe such as thermolysin, leukotriene A4 hydrolase relatives, and cowrins. Noteworthy, gluzincins mostly contain a glutamate as third characteristic zinc ligand, whereas minigluzincins have a histidine. Sequence and structural similarity further allowed us to ascertain that minigluzincins are very similar to the catalytic domains of integral membrane MPs of the MEROPS database families M48 and M56, such as FACE1, HtpX, Oma1, and BlaR1/MecR1, which are provided with trans-membrane helices flanking or inserted into a minigluzincin-like catalytic domain. In a time where structural biochemistry of integral-membrane proteins in general still faces formidable challenges, the minigluzincin soluble minimal scaffold may contribute to our understanding of the working mechanisms of these membrane MPs and to the design of novel inhibitors through structure-aided rational drug design approaches.

scholarly journals Binding of Azobenzene and p-Diaminoazobenzene to the Human Voltage-Gated Sodium Channel NaV1.4

2020 ◽  
Author(s):  
Vito F. Palmisano ◽  
Carlos Gómez-Rodellar ◽  
Hannah Pollak ◽  
Gustavo Cárdenas ◽  
Ben Corry ◽  
...  
Keyword(s):  
Electrostatic Interactions ◽  
Hydrophobic Interactions ◽  
Binding Pocket ◽  
Internal Cavity ◽  
Amino Groups ◽  
Voltage Gated ◽  
Accelerated Molecular Dynamics ◽  
Binding Pockets ◽  
Voltage Gated Ion Channels ◽  
Dynamics Simulations

The activity of voltage-gated ion channels can be controlled by the binding of photoswitches inside their internal cavity and subsequent light irradiation. We investigated the binding of azobenzene and p-diaminoazobenzene to the human Na<sub>V</sub>1.4 channel in the inactivated state by means of Gaussian accelerated molecular dynamics simulations and free-energy computations. Three stable binding pockets were identified for each of the two photoswitches. In all the cases, the binding is controlled by the balance between the favorable hydrophobic interactions of the ligands with the nonpolar residues of the protein and the unfavorable polar solvation energy. In addition, electrostatic interactions between the ligand and the polar aminoacids are also relevant for p-diaminoazobenzene due to the presence of the amino groups on the benzene moieties. These groups participate in hydrogen bonding in the most favorable binding pocket and in long-range electrostatic interactions in the other pockets. The thermodinamically preferred binding sites found for both photoswitches are close to the selectivity filter of the channel. Therefore, it is very likely that the binding of these ligands will induce alterations in the ion conduction through the channel.

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