Role of Electronegative Atom Present on Ligand Backbone and Substrate Binding Mode on Catecholase- and Phosphatase-Like Activities of Dinuclear NiIIComplexes: A Theoretical Support

To explore the sequence context-dependent nature of the human immunodeficiency virus type 1 (HIV-1) protease’s specificity and to provide a rationale for viral mutagenesis to study the potential role of the nucleocapsid (NC) processing in HIV-1 replication, synthetic oligopeptide substrates representing the wild-type and modified versions of the proximal cleavage site of HIV-1 NC were assayed as substrates of the HIV-1 protease (PR). The S1′ substrate binding site of HIV-1 PR was studied by an in vitro assay using KIVKCF↓NCGK decapeptides having amino acid substitutions of N17 residue of the cleavage site of the first zinc-finger domain, and in silico calculations were also performed to investigate amino acid preferences of S1′ site. Second site substitutions have also been designed to produce “revertant” substrates and convert a non-hydrolysable sequence (having glycine in place of N17) to a substrate. The specificity constants obtained for peptides containing non-charged P1′ substitutions correlated well with the residue volume, while the correlation with the calculated interaction energies showed the importance of hydrophobicity: interaction energies with polar residues were related to substantially lower specificity constants. Cleavable “revertants” showed one residue shift of cleavage position due to an alternative productive binding mode, and surprisingly, a double cleavage of a substrate was also observed. The results revealed the importance of alternative binding possibilities of substrates into the HIV-1 PR. The introduction of the “revertant” mutations into infectious virus clones may provide further insights into the potential role of NC processing in the early phase of the viral life-cycle.

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Hepatic 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase. The role of surface loop basic residues in substrate binding to the fructose-2,6-bisphosphatase domain.

Journal of Biological Chemistry ◽

10.1016/s0021-9258(19)36651-7 ◽

1992 ◽

Vol 267 (30) ◽

pp. 21588-21594

Author(s):

L Li ◽

K Lin ◽

J Pilkis ◽

J.J. Correia ◽

S.J. Pilkis

Keyword(s):

Substrate Binding ◽

Surface Loop

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The role of Glu196 in the environment around the substrate binding site of leucine aminopeptidase fromStreptomyces griseus

FEBS Letters ◽

10.1016/j.febslet.2006.01.014 ◽

2006 ◽

Vol 580 (3) ◽

pp. 912-917 ◽

Cited By ~ 6

Author(s):

Jiro Arima ◽

Yoshiko Uesugi ◽

Misugi Uraji ◽

Masaki Iwabuchi ◽

Tadashi Hatanaka

Keyword(s):

Binding Site ◽

Leucine Aminopeptidase ◽

Substrate Binding ◽

Substrate Binding Site

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Coherence Effects in Multiple Medium-Induced Radiation

Proceedings ◽

10.3390/proceedings2019010011 ◽

2019 ◽

Vol 10 (1) ◽

pp. 11

Author(s):

Fabio Dominguez ◽

Jose Guilherme Milhano ◽

Carlos A. Salgado ◽

Konrad Tywoniuk ◽

Victor Vila

Keyword(s):

Time Scales ◽

Survival Probability ◽

Jet Quenching ◽

Close Correspondence ◽

Gluon Emission ◽

Classical Description ◽

Theoretical Support ◽

Coherence Effects ◽

Hard Gluon

In the first part of this work we study the color coherence phenomenon by considering the well-known quark-antiquark antenna with an in-medium hard gluon emission and an extra very soft emission outside it—double antenna. By discussing the coherence effects in terms of the survival probability, we generalize previous studies of the antenna radiation to the case of more than two emitters. After providing support to the jet quenching picture with effective emitters in the QCD cascade, we present a novel setup of an antenna splitting inside the medium taking into account the finite formation time of the dipole, which turns out to be an important scale. We read into the role of coherence and the relevant time scales which control the scenario, while also providing theoretical support for vacuum-like emissions early in the medium. Finally, by mapping the spectrum of in-medium splittings through the corresponding kinematical Lund diagram, we appreciate regimes of a close correspondence to a semi-classical description.

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Crystal structures of Ca2+–calmodulin bound to NaV C-terminal regions suggest role for EF-hand domain in binding and inactivation

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1818618116 ◽

2019 ◽

Vol 116 (22) ◽

pp. 10763-10772 ◽

Cited By ~ 10

Author(s):

Bernd R. Gardill ◽

Ricardo E. Rivera-Acevedo ◽

Ching-Chieh Tung ◽

Filip Van Petegem

Keyword(s):

Crystal Structure ◽

Binding Sites ◽

Binding Mode ◽

Conformational Switch ◽

Channel Inactivation ◽

Dependent Inactivation ◽

Ef Hand ◽

Inherited Arrhythmia ◽

A Site

Voltage-gated sodium (NaV) and calcium channels (CaV) form targets for calmodulin (CaM), which affects channel inactivation properties. A major interaction site for CaM resides in the C-terminal (CT) region, consisting of an IQ domain downstream of an EF-hand domain. We present a crystal structure of fully Ca2+-occupied CaM, bound to the CT of NaV1.5. The structure shows that the C-terminal lobe binds to a site ∼90° rotated relative to a previous site reported for an apoCaM complex with the NaV1.5 CT and for ternary complexes containing fibroblast growth factor homologous factors (FHF). We show that the binding of FHFs forces the EF-hand domain in a conformation that does not allow binding of the Ca2+-occupied C-lobe of CaM. These observations highlight the central role of the EF-hand domain in modulating the binding mode of CaM. The binding sites for Ca2+-free and Ca2+-occupied CaM contain targets for mutations linked to long-QT syndrome, a type of inherited arrhythmia. The related NaV1.4 channel has been shown to undergo Ca2+-dependent inactivation (CDI) akin to CaVs. We present a crystal structure of Ca2+/CaM bound to the NaV1.4 IQ domain, which shows a binding mode that would clash with the EF-hand domain. We postulate the relative reorientation of the EF-hand domain and the IQ domain as a possible conformational switch that underlies CDI.

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Role of Cytochrome P450 in Tulip Bulb Probed by Substrate-Binding Studies

Pesticide Science ◽

10.1002/ps.2780360105 ◽

1992 ◽

Vol 36 (1) ◽

pp. 27-30 ◽

Cited By ~ 4

Author(s):

Steven L. Kelly ◽

Aysegul Topal ◽

Ian Barnett ◽

Diane E. Kelly ◽

George A. F. Hendry

Keyword(s):

Cytochrome P450 ◽

Substrate Binding ◽

Binding Studies ◽

Tulip Bulb

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The clpB gene of Bifidobacterium breve UCC 2003: transcriptional analysis and first insights into stress induction

Microbiology ◽

10.1099/mic.0.28176-0 ◽

2005 ◽

Vol 151 (9) ◽

pp. 2861-2872 ◽

Cited By ~ 33

Author(s):

Marco Ventura ◽

John G. Kenny ◽

Ziding Zhang ◽

Gerald F. Fitzgerald ◽

Douwe van Sinderen

Keyword(s):

3D Structure ◽

Binding Mode ◽

Dna Interaction ◽

Transcriptional Analysis ◽

Amino Acid Residues ◽

Mobility Shift ◽

Bifidobacterium Breve ◽

Gel Mobility Shift ◽

Slot Blot Analysis

The so-called clp genes, which encode components of the Clp proteolytic complex, are widespread among bacteria. The Bifidobacterium breve UCC 2003 genome contains a clpB gene with significant homology to predicted clpB genes from other members of the Actinobacteridae group. The heat- and osmotic-inducibility of the B. breve UCC 2003 clpB homologue was verified by slot-blot analysis, while Northern blot and primer extension analyses showed that the clpB gene is transcribed as a monocistronic unit with a single promoter. The role of a hspR homologue, known to control the regulation of clpB and dnaK gene expression in other high G+C content bacteria was investigated by gel mobility shift assays. Moreover the predicted 3D structure of HspR provides further insight into the binding mode of this protein to the clpB promoter region, and highlights the key amino acid residues believed to be involved in the protein–DNA interaction.

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