Structural relationships in the two-zinc insulin hexamer

1979 ◽  
Vol 57 (6) ◽  
pp. 469-479 ◽  
Author(s):  
E. J. Dodson ◽  
G. G. Dodson ◽  
D. C. Hodgkin ◽  
C. D. Reynolds
Keyword(s):  
Crystal Structure ◽  
Biological Activity ◽  
Main Chain ◽  
Side Chain ◽  
C Terminus ◽  
Structural Relationships ◽  
N Terminus ◽  
Independent Molecules ◽  
A Chain ◽  
Resolution Data

The refinement of the crystal structure of two-Zn pig insulin using 1.5-Å (1 Å = 0.1 nm) resolution data by Fourier and fast Fourier least-squares methods allows us to make detailed comparisons between the two independent molecules present in the two-Zn insulin dimer and to describe their interactions in the monomer, dimer, and hexamer. The main chain structures for the two molecules agree well except at the N terminus of the A chain and the C terminus of the B chain. The residues along the line of the local two-fold axes, apart from theB25 side chain, conform extremely closely to the two-fold symmetry, although the discrepancies are much more apparent away from this axis. The ability of the insulin molecule to adopt different conformations may be an important factor in the expression of its biological activity.

scholarly journals The semisynthesis of fragments corresponding to residues 66-104 of horse heart cytochrome c

1979 ◽  
Vol 179 (1) ◽  
pp. 169-182 ◽  
Author(s):  
C J Wallace ◽  
R E Offord
Keyword(s):  
Biological Activity ◽  
Amino Acid ◽  
Cytochrome C ◽  
Amino Acid Sequences ◽  
Side Chain ◽  
Horse Heart Cytochrome ◽  
Natural Sequence ◽  
C Terminus ◽  
N Terminus ◽  
Horse Heart Cytochrome C

We describe the N epsilon-acetimidylation of horse heart cytochrome c with retention of biological activity, the cleavage of the modified protein by CNBr, the separation of the fragments, and their further side-chain protection. We describe the manipulation of the amino acid sequences of the fragments by stepwise semisynthetic methods. We have prepared fragments corresponding to residues 66-78 and 66-79 of the protein, as well as the [Asp66] analogue of fragment 66-79. We have prepared the natural sequence and the [o-fluoro-Phe82] analogue of the fragment corresponding to residues 81-104 of the protein, and the [N epsilon-trifluoroacetyl-Lys79], the [N epsilon-dinitrophenyl-Lys79] and the [S-acetamidomethyl-Cys79] analogues of fragment 79-104, and the [N epsilon-Cbz-Lys81] analogue of fragment 80-104. We have coupled back the fragments of natural sequence to form a semisynthetic fragment corresponding to residues 66-104 of the protein. Modified fragments were also coupled to give analogues of the 66-104-residue sequence. In every case the homoserine residue representing methionine-80 was removed from the C-terminus of the 66-80-residue fragment and replaced by methionine on the N-terminus of the 81-104 residue fragment during the preparation of the fragments for coupling. The semisynthetic fragments are ready for specific deprotection and further coupling. We have coupled one such fragment to the (1-65)-peptide to produce semisynthetic [Hse65]cytochrome c. The product has satisfactory characteristics on chemical analysis, and on assay of its biological activity.

Molecular Modeling and Virtual Screening of Molecular Inhibitors for Leptospiral Collagenase

2021 ◽  
Author(s):  
Vikram Kumar ◽  
Nagesh Srikaku ◽  
Veeranarayanan Surya Aathmanathan ◽  
Padikara K Satheeshkumar ◽  
Madanan Gopalakrishnan Madathiparambil ◽  
...  
Keyword(s):  
Crystal Structure ◽  
Molecular Modeling ◽  
Active Site ◽  
Binding Sites ◽  
Catalytic Site ◽  
Simulation Studies ◽  
C Terminus ◽  
Ligand Binding Sites ◽  
N Terminus ◽  
The Stability

Abstract Collagenase is a virulence factor which facilitates the invasion of pathogenic Leptospira into the host. In the present study, the model of Leptopsiral collagenase was constructed by employing threading method with the crystal structure of collagenase G. Three ligand binding sites at N- terminus, catalytic site and C-terminus were predicted by Metapocket server. Among sixty seven inhibitors from the ChEBI and Zinc databases, Protohypericin is predicted as the best inhibitor since it binds at the catalytic site of Leptopsiral collagenase. Molecular dynamic simulation studies validated the stability of interaction between the active site of Leptospiral collagenase and Protohypericin. The docking and molecular simulation studies corroborated the potential of the ligand to curb leptospiral infection.

scholarly journals Does Cysteine Rule (CysR) Complete the CendR Principle? Increase in Affinity of Peptide Ligands for NRP-1 Through the Presence of N-Terminal Cysteine

Biomolecules ◽  
2020 ◽  
Vol 10 (3) ◽  
pp. 448 ◽  
Author(s):  
Anna K. Puszko ◽  
Piotr Sosnowski ◽  
Françoise Raynaud ◽  
Olivier Hermine ◽  
Gérard Hopfgartner ◽  
...  
Keyword(s):  
Peptide Ligands ◽  
Side Chain ◽  
Amino Group ◽  
Structure Activity ◽  
C Terminus ◽  
Neuropilin 1 ◽  
Ic50 Value ◽  
N Terminus ◽  
Terminal Amino ◽  
Relationship Of

The structure-activity relationship of branched H-Lys(hArg)-Dab-Dhp-Arg-OH sequence analogues, modified with Cys-Asp or Cys at N-terminal amino acids (Lys, hArg), in VEGF-A165/Neuropilin-1 complex inhibition is presented. The addition of Cys residue led to a 100-fold decrease in the IC50 value, compared to the parent peptide. The change occurred regardless of coupling Cys to the free N-terminal amino group present in the main or the side chain. A few analogues extended by the attachment of Cys at the N-terminus of several potent NRP-1 peptide ligands documented in the literature are also presented. In all studied cases, the enhancement of inhibitory properties after the addition of Cys at the N-terminus is observed. It is particularly evident for the tetrapeptide derived from the C-terminus of VEGF-A165 (KPRR), suggesting that extending the K/RXXK/R motif (CendR) with the Cys moiety can significantly improve affinity to NRP-1 of CendR peptides.

(+)-3,12-Dioxo-5β-cholanic acid: hydrogen bonding in a diketo bile-acid derivative

2006 ◽  
Vol 62 (7) ◽  
pp. o2641-o2643 ◽  
Author(s):  
Elizabeth M. Kikolski ◽  
Mark Davison ◽  
Roger A. Lalancette ◽  
Hugh W. Thompson
Keyword(s):  
Crystal Structure ◽  
Hydrogen Bonding ◽  
Bile Acid ◽  
Hydrogen Bonds ◽  
Side Chain ◽  
Asymmetric Unit ◽  
Independent Molecules ◽  
Chain Conformations ◽  
Cholanic Acid ◽  
Close Contacts

The asymmetric unit of the title crystal structure, C24H36O4, contains two independent molecules, differing only in their side-chain conformations and linked though O—H...O hydrogen bonds by carboxyl pairing [O...O = 2.6715 (17) and 2.6544 (17) Å; O—H...O = 170 and 179°]. Six intermolecular C—H...O=C close contacts were found.

scholarly journals Crystal structure of morpholin-4-ium cinnamate

2015 ◽  
Vol 71 (11) ◽  
pp. o850-o851 ◽  
Author(s):  
Graham Smith
Keyword(s):  
Crystal Structure ◽  
Hydrogen Bond ◽  
Hydrogen Bonding ◽  
Cinnamic Acid ◽  
Torsion Angle ◽  
Chain Structure ◽  
Side Chain ◽  
Hydrogen Bonding Interaction ◽  
Bonding Interaction ◽  
A Chain

In the anhydrous salt formed from the reaction of morpholine with cinnamic acid, C4H10NO+·C9H7O2−, the acid side chain in thetrans-cinnamate anion is significantly rotated out of the benzene plane [C—C—C— C torsion angle = 158.54 (17)°]. In the crystal, one of the the aminium H atoms is involved in an asymmetric three-centre cation–anion N—H...(O,O′)R12(4) hydrogen-bonding interaction with the two carboxylate O-atom acceptors of the anion. The second aminium-H atom forms an inter-species N—H...Ocarboxylatehydrogen bond. The result of the hydrogen bonding is the formation of a chain structure extending along [100]. Chains are linked by C—H...O interactions, forming a supramolecular layer parallel to (01-1).

scholarly journals Gene cloning and construction of prokaryotic and plant expression vectors of RICIN-A-Chain/PAP-S1 fusion protein and its inhibition of protein synthesis

2016 ◽  
Author(s):  
Yasser S. Hassan ◽  
Sherry L. Ogg
Keyword(s):  
Fusion Protein ◽  
Expression Vectors ◽  
Single Chain ◽  
Antiviral Protein ◽  
Ricin A Chain ◽  
C Terminus ◽  
N Terminus ◽  
A Cell ◽  
A Chain ◽  
Ricin A

AbstractPokeweed antiviral protein (PAP) is a single-chain ribosome-inactivating protein that exists in several forms isolated from various organs and at different stages of development of Phytolacca americana (pokeweed). In this study, PAP-S1, one of the two known isoforms found in seeds, was isolated and PCR amplified using primers based on the known mRNA of PAP-S2, the other known form found in seeds. The complete cDNA encoding PAP-S1 was determined here for the first time. PAP-S1 is a potent antiviral protein with many potential clinical applications. However, it was found to be dosage dependent with observed side effects at high dosage. In this study, we report the production of a recombinant antiviral peptide-fusion protein between Ricin A-chain and PAP-S1. The peptide-fusion recombinant proteins Ricin-A-Chain/PAP-S1 and PAP-S1/Ricin-A-Chain were generated by joining the Nterminus of PAP-S1 to the C-terminus of Ricin A-chain and the C-terminus of PAP-S1 to the N-terminus of Ricin A-chain respectively, and were expressed in an Escherichia coli cell free expression systems. The peptide-fusion recombinant protein Ricin-A-Chain/PAP-S1 (F2) was found to be more active than the PAPS1/Ricin-A-chain (F1) and similar to PAP-S1 in a cell free prokaryotic environment, and both showed much stronger activity in a cell free eukaryotic environment. The DNA sequence of the complete cDNA of PAP-S1 and of the peptide-fusion protein Ricin-A-Chain/PAP-S1 with the PAP-S1 signal peptide at the N-terminus of Ricin Achain were inserted in plant destination binary vectors for A. tumefaciens mediated transformation. It is the authors’ opinion that additional research should be done in order to determine both cytotoxicity and selectivity of fusion protein F2 compared to PAP-S1, as it could be a viable, more potent and less cytotoxic alternative to PAPS1 alone at high dosage, for both agricultural and therapeutic applications.

scholarly journals Crystal structure of 2,5-dimethyl-3-(2-methylphenylsulfonyl)-1-benzofuran

2014 ◽  
Vol 70 (11) ◽  
pp. o1181-o1182
Author(s):  
Hong Dae Choi ◽  
Uk Lee
Keyword(s):  
Crystal Structure ◽  
Hydrogen Bonds ◽  
Title Compound ◽  
Ring System ◽  
Asymmetric Unit ◽  
Π Interactions ◽  
Compound C ◽  
Centroid Distance ◽  
Independent Molecules ◽  
A Chain

The title compound, C17H16O3S, crystallized with two independent molecules (AandB) in the asymmetric unit. The dihedral angle between the benzofuran ring system [r.m.s. deviation of 0.013 (1) forAand 0.009 (1) Å forB] and the 2-methylphenyl ring is 83.88 (5) forAand 86.94 (5)° forB. In the crystal, theBmolecules are linked into a chain along theb-axis direction by C—H...O hydrogen bonds. TheAmolecules are connected on either side of this chain by further C—H...O hydrogen bonds. These chains are linkedviaC—H...π interactions, forming sheets parallel to (100). There are also very weak π–π interactions present [centroid–centroid distance = 3.925 (11) Å] involvingthe 2-methylphenyl rings of neighbouringAandBmolecules.

5-Ethynyl-2′-deoxycytidine: a DNA building block with a `clickable' side chain

2012 ◽  
Vol 68 (10) ◽  
pp. o395-o398 ◽  
Author(s):  
Frank Seela ◽  
Hui Mei ◽  
Hai Xiong ◽  
Simone Budow ◽  
Henning Eickmeier ◽  
...  
Keyword(s):  
Crystal Structure ◽  
Hydrogen Bonding ◽  
Building Block ◽  
Title Compound ◽  
Crystalline State ◽  
Three Dimensional ◽  
Side Chain ◽  
Sugar Residue ◽  
A Chain ◽  
Dimensional Crystal

The title compound [systematic name: 4-amino-1-(2-deoxy-β-D-erythro-pentofuranosyl)-5-ethynylpyrimidin-2(1H)-one], C11H13N3O4, shows two conformations in the crystalline state. The N-glycosylic bonds of both conformers adopt similar conformations, with χ = −149.2 (1)° for conformer (I-1) and −151.4 (1)° for conformer (I-2), both in theantirange. The sugar residue of (I-1) shows a C2′-endoenvelope conformation (2E,S-type), withP= 164.7 (1)° and τm= 36.9 (1)°, while (I-2) shows a major C3′-exosugar pucker (C3′-exo-C2′-endo,3T2,S-type), withP= 189.2 (1)° and τm= 33.3 (1)°. Both conformers participate in the formation of a layered three-dimensional crystal structure with a chain-like arrangement of the conformers. The ethynyl groups do not participate in hydrogen bonding, but are arranged in proximal positions.

scholarly journals Crystal structure and Hirshfeld surface analysis of 3-(cyclopropylmethoxy)-4-(difluoromethoxy)-N-(pyridin-2-ylmethyl)benzamide

2019 ◽  
Vol 75 (10) ◽  
pp. 1515-1518
Author(s):  
G. Artheswari ◽  
V. Maheshwaran ◽  
N. Gautham
Keyword(s):  
Crystal Structure ◽  
Hydrogen Bonds ◽  
Pyridine Ring ◽  
Three Dimensional ◽  
Hirshfeld Surface ◽  
Dimensional Structure ◽  
Side Chain ◽  
Asymmetric Unit ◽  
Compound C ◽  
Independent Molecules

The title compound, C18H18F2N2O3, crystallizes with two independent molecules (A and B) in the asymmetric unit. They differ essentially in the orientation of the pyridine ring with respect to the benzene ring; these two rings are inclined to each other by 53.3 (2)° in molecule A and by 72.9 (2)° in molecule B. The 3-(cyclopropylmethoxy) side chain has an extended conformation in both molecules. The two molecules are linked by a pair of C—H...O hydrogen bonds and two C—H...π interactions, forming an A–B unit. In the crystal, this unit is linked by N—H...O hydrogen bonds, forming a zigzag –A–B–A–B– chain along [001]. The chains are linked by C—H...N and C—H...F hydrogen bonds to form layers parallel to the ac plane. Finally, the layers are linked by a third C—H...π interaction, forming a three-dimensional structure. The major contributions to the Hirshfeld surface are those due to H...H contacts (39.7%), followed by F...H/H...F contacts (19.2%).

Analogues of cholecystokinin methylated in the side chain of carboxyterminal phenylalanine

1991 ◽  
Vol 56 (12) ◽  
pp. 2991-2998 ◽  
Author(s):  
Jan Hlaváček ◽  
Jana Pírková ◽  
Pavel Majer ◽  
Miroslava Žertová ◽  
Lenka Maletínská ◽  
...  
Keyword(s):  
Biological Activity ◽  
Gall Bladder ◽  
Side Chain ◽  
Preparative Hplc ◽  
Aromatic Side Chain ◽  
C Terminus ◽  
Bladder Contraction ◽  
Phenylalanine Residue

In the course of our study on cholecystokinin (CCK) a series of Boc-CCK-7 was synthesized. Their carboxyterminal part was modified by phenylalanine derivatives containing 2 or 4 and 2,6 or 2,4,6 methylated aromatic side-chain. During the synthesis, the racemic phenylalanine derivatives were used and peptides containing either L- or D- methylated phenylalanine were separated using a preparative HPLC. Gall bladder contraction, anorectic, sedative and analgetic bioassays of these analogues revealed that all of them behaved as CCK-8 agonists. While the analogues containing L-form of the methylated phenylalanines had almost the same potency (80% - 130%) in comparison to CCK-8, the presence of the D-form decreased the biological activity of corresponding analogues to 8 – 62% of the CCK-8 potency. These results are in agreement with the suggestion that phenylalanine residue in C-terminus takes part in biological activity transduction only.

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