Design and Crystal Structures of Triple Helicates with Crystallographic IdealizedD3Symmetry:  The Role of Side Chain Effect on Crystal Packing

2002 ◽  
Vol 41 (23) ◽  
pp. 5978-5985 ◽  
Author(s):  
Guo Dong ◽  
Pang Ke-liang ◽  
Duan Chun-ying ◽  
He Cheng ◽  
Meng Qing-jin
Keyword(s):  
Crystal Structures ◽  
Crystal Packing ◽  
Side Chain

Similarities and differences in the crystal packing of halogen-substituted indole derivatives

2018 ◽  
Vol 74 (4) ◽  
pp. 376-384 ◽  
Author(s):  
Rahul Shukla ◽  
Paramveer Singh ◽  
Piyush Panini ◽  
Deepak Chopra
Keyword(s):  
Quantum Theory ◽  
Crystal Structures ◽  
Crystal Packing ◽  
Topological Analysis ◽  
Indole Derivatives ◽  
Π Interactions ◽  
Supramolecular Motifs ◽  
Exchange Repulsion ◽  
Similarities And Differences

The role of different intermolecular interactions in the crystal structures of halogen-substituted indoles which are fused with six-membered or seven-membered cyclic rings is investigated here. Several crystal structures show isostructural characteristics due to the presence of similar supramolecular motifs. In the absence of any strong hydrogen bonds, the molecular packing of reported structures is primarily stabilized by the presence of non-classical N—H...π and C—H...π interactions in addition to C—H...X (X = F/Cl/Br) interactions. The nature and energetics of primary and secondary dimeric motifs are partitioned into the electrostatics, polarization, dispersion and exchange–repulsion components using the PIXEL method. Short and directional N—H...π interactions are further explored by a topological analysis of the electron density based on quantum theory of atoms in molecules.

Structural and Functional Evidence on the Role of Sulfated Tyrosine Residues In Glycoprotein Ib Binding to α-Thrombin Exosites

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 326-326
Author(s):  
Alessandro Zarpellon ◽  
Reha Celikel ◽  
Richard McClintock ◽  
James R. Roberts ◽  
G. Loredana Mendolicchio ◽  
...  
Keyword(s):  
Crystal Structures ◽  
Conflicts Of Interest ◽  
Crystal Packing ◽  
Binding Activity ◽  
Wild Type ◽  
Soluble Complex ◽  
Structural Explanation ◽  
Amino Terminal

Abstract Abstract 326 In spite of two known crystal structures, the mechanisms supporting the interaction between the amino terminal domain of glycoprotein (GP) Ibα (GPIb-N) and α-thrombin (FIIa) are still debated, and a controversial issue concerns the involvement of FIIa exosites I and II in binding. Competition for exosite I could influence processes important for hemostasis and thrombosis. Both known crystal structures show two independent contact interfaces between GPIb-N and bound FIIa in a conformation that involves each exosite interacting with a different GPIb-N molecule. This notwithstanding, a majority of investigators in the field has concluded that exosite II is solely required for FIIa binding to GPIb-N, suggesting that the interface with exosite I is the consequence of crystal packing. The goal of this work was to probe experimentally the role of FIIa exosites in GPIb-N binding. Human GPIb-N contains three Tyr residues (at positions 276, 278 and 279) that can undergo post-translational sulfation (sulfated Tyr = Tys), although this was not the case for Tyr278 in the known crystal structures. To address this discrepancy, we expressed GPIb-N in Drosophila cells - which endogenously contain a single tyrosylprotein sulfotransferase (TPST) gene - co-transfected with human TPST-2, and showed that we could obtain different GPIb-N species with 0 to 3 sulfate moles/protein moles. Using these different GPIb-N forms immobilized onto a surface plasmon resonance (SPR) chip, we determined that the kD of human FIIa binding decreased from 1290 to 89 nM going from 0 to 3 sulfate moles/protein moles. We crystallized the fully sulfated GPIb-N complexed with FIIa and found that Tys278 established contacts not previously seen with exosite II (residues Arg35 and Lys236), thus explaining the contribution of full sulfation to maximal binding efficiency. To establish the effect of TPST-2 on the process of sulfation, we compared the affinity of FIIa binding to distinct wild type GPIb-N species of known sulfate content with that to GPIb-N mutants containing distinct single, double or triple Tyr “Phe substitutions (Phe differs from Tyr for the lack of an OH group and cannot be sulfated) in which the identity of Tys residues could be established. We found that TPST-2 favors Tyr sulfation in the order 276–278-279, which is more efficient for a complete process than the order 276–279 predominant in the absence of TPST-2. We then used different Tyr "Phe (Y to F) mutants to evaluate the effects of the substitution preventing sulfation on FIIa binding to GPIb-N in solution or immobilized onto a SPR chip. We fount that the Y276F mutant had no capacity to form a soluble complex with FIIa, while Y279F could complex about as much FIIa as fully sulfated wild type GPIb-N (82 vs 99% FIIa incorporation). Of note, both Y276F and Y279F mutants had a complete to nearly complete loss of FIIa binding activity in the SPR system. In the crystal structure, the sulfate group on Tys279 establishes three close contacts (3.1, 3.3, 2.8 □) with Trp148 in a FIIa loop neighboring exosite I. On the other hand, Tys276 has closer contacts than Tys279 with residues in exosite II, suggesting that the latter may be sufficient for FIIa binding when GPIb-N is in solution but not immobilized onto a surface. To confirm this hypothesis, we used specific aptamer inhibitors of FIIa exosite II (HD22) or I (HD1) and found that the latter, similar to the Y279F substitution, indeed had no effect on FIIa-GPIb-N soluble complex formation (thus ruling out possible allosteric effects on exosite II influencing GPIb-N binding) but completely prevented FIIa binding to immobilized GPIb-N. Of note, as shown by crystallographic evidence, bound HD1 alters the orientation of Trp148 in manner that would oppose the interaction with Tys279 in GPIb-N, providing a structural explanation for the similar functional effects of the mutation and the inhibitor. Finally, we expressed transgenically wild type or Y279F mutant human GPIbα to replace the homologous chain in the GPIb-IX-V complex of murine platelets and showed that the mutation almost completely impairs FIIa binding to platelets, which is also prevented by inhibition of exosite I with HD1. These results provide functional evidence and a structural explanation for a key role of exosite I, concurrently with exosite II, for FIIa binding to GPIbα. Additional studies are now demonstrating that interfering with this interaction modifies responses to vascular injury in vivo. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Quantitative Lattice Energy Analysis of Intermolecular Interactions in Crystal Structures of Some Benzimidazole Derivatives

2020 ◽  
Vol 5 (1-2) ◽  
pp. 53-62
Author(s):  
Gopal Sharma ◽  
Rajni Kant
Keyword(s):  
Crystal Structures ◽  
Intermolecular Interactions ◽  
Energy Analysis ◽  
Crystal Packing ◽  
Lattice Energy ◽  
Molecular Packing ◽  
Benzimidazole Derivatives ◽  
Intermolecular Hydrogen Bonds ◽  
Centrosymmetric Dimers

The benzimidazole moiety found in a large number of biologically important drugs has not been completely realized as yet in respect of its strength and directionality of its molecular interactions. To understand the role played by the intermolecular interactions in the benzimidazole derivatives, lattice energy of a series of five important molecules has been computed and results accrued thereof have been discussed. Analysis of molecular packing based on the intermolecular interaction energies suggests existence of different molecular pairs that play an important role in the stabilization of the crystal structures. Interaction energy analysis of such motifs reveals that intermolecular interactions of the type N-H…N and C-H…N happen to be the major contributors to the stabilization of molecular packing in the unit cell. N-H…π and C-H…π type edge-to-face stacking interactions also contribute significantly to the stabilization of crystal packing. The pairs of N-H…N intermolecular hydrogen bonds link the molecules into centrosymmetric dimers making a contribution of -14 to -18.52 kcal/mol towards stabilization, whereas C-H…N bonds link the molecules into dimers in the energy range of -2 to -5 kcal/mol. Additionally, the role of π…π interactions has also been investigated in molecular stabilization.

Crystal packing and melting temperatures of small oxalate esters: the role of C—H...O hydrogen bonding

2011 ◽  
Vol 67 (6) ◽  
pp. 525-534 ◽  
Author(s):  
Sumy Joseph ◽  
Ranganathan Sathishkumar ◽  
Sudarshan Mahapatra ◽  
Gautam R. Desiraju
Keyword(s):  
Crystal Structures ◽  
Room Temperature ◽  
Crystal Packing ◽  
The Other ◽  
Methyl Ethyl ◽  
Melting Points ◽  
Dimethyl Oxalate ◽  
Melting Temperatures ◽  
Entropic Contribution

The simple dialkyl oxalates are generally liquids at room temperature except for dimethyl and di-tert-butyl oxalate which melt at 327 and 343 K. The crystal structures of diethyl, di-iso-propyl, di-n-butyl, di-tert-butyl and methyl ethyl oxalates were determined. The liquid esters were crystallized using the cryocrystallization technique. A comparison of the intermolecular interactions and packing features in these crystal structures was carried out. The crystal structure of dimethyl oxalate was redetermined at various temperatures. The other compounds were also studied at several temperatures in order to assess the attractive nature of the hydrogen bonds therein. A number of moderate to well defined C—H...O interactions account for the higher melting points of the two solid esters. Additionally, a diminished entropic contribution ΔS m in di-tert-butyl oxalate possibly increases the melting point of this compound further.

The role of non-covalent intermolecular interactions on the diversity of crystal packing in supramolecular dihalopyridine–silver(i) nitrate complexes

CrystEngComm ◽  
2020 ◽  
Vol 22 (45) ◽  
pp. 7962-7974
Author(s):  
Sunčica Roca ◽  
Lucija Hok ◽  
Robert Vianello ◽  
Mladen Borovina ◽  
Marijana Đaković ◽  
...  
Keyword(s):  
Dft Calculations ◽  
Crystal Structures ◽  
Intermolecular Interactions ◽  
Crystal Packing ◽  
Nitrate Complexes

The crystal structures of six novel Ag+ complexes with NO3− and dihalopyridines revealed intriguing differences that were interpreted by DFT calculations.

Structural and functional studies of Bacillus stearothermophilus serine hydroxymethyltransferase: the role of Asn341, Tyr60 and Phe351 in tetrahydrofolate binding

2009 ◽  
Vol 418 (3) ◽  
pp. 635-642 ◽  
Author(s):  
Vinitha R. Pai ◽  
V. Rajaram ◽  
Shveta Bisht ◽  
B. S. Bhavani ◽  
N. Appaji Rao ◽  
...  
Keyword(s):  
Crystal Structures ◽  
Bacillus Stearothermophilus ◽  
Side Chain ◽  
Side Reactions ◽  
Type I ◽  
Functional Studies ◽  
Binary Complexes ◽  
Dependent Activity ◽  
In The Wild

SHMT (serine hydoxymethyltransferase), a type I pyridoxal 5′-phosphate-dependent enzyme, catalyses the conversion of L-serine and THF (tetrahydrofolate) into glycine and 5,10-methylene THF. SHMT also catalyses several THF-independent side reactions such as cleavage of β-hydroxy amino acids, transamination, racemization and decarboxylation. In the present study, the residues Asn341, Tyr60 and Phe351, which are likely to influence THF binding, were mutated to alanine, alanine and glycine respectively, to elucidate the role of these residues in THF-dependent and -independent reactions catalysed by SHMT. The N341A and Y60A bsSHMT (Bacillus stearothermophilus SHMT) mutants were inactive for the THF-dependent activity, while the mutations had no effect on THF-independent activity. However, mutation of Phe351 to glycine did not have any effect on either of the activities. The crystal structures of the glycine binary complexes of the mutants showed that N341A bsSHMT forms an external aldimine as in bsSHMT, whereas Y60A and F351G bsSHMTs exist as a mixture of internal/external aldimine and gem-diamine forms. Crystal structures of all of the three mutants obtained in the presence of L-allo-threonine were similar to the respective glycine binary complexes. The structure of the ternary complex of F351G bsSHMT with glycine and FTHF (5-formyl THF) showed that the monoglutamate side chain of FTHF is ordered in both the subunits of the asymmetric unit, unlike in the wild-type bsSHMT. The present studies demonstrate that the residues Asn341 and Tyr60 are pivotal for the binding of THF/FTHF, whereas Phe351 is responsible for the asymmetric binding of FTHF in the two subunits of the dimer.

Structural, magnetic and Mössbauer spectroscopic studies of the [Fe(3-bpp)2](CF3COO)2 complex: role of crystal packing leading to an incomplete Fe(ii) high spin ⇋ low spin transition

CrystEngComm ◽  
2021 ◽  
Vol 23 (15) ◽  
pp. 2854-2861
Author(s):  
Kristian Handoyo Sugiyarto ◽  
Djulia Onggo ◽  
Hiroki Akutsu ◽  
Varimalla Raghavendra Reddy ◽  
Hari Sutrisno ◽  
...  
Keyword(s):  
High Spin ◽  
Crystal Packing ◽  
Spin Transition ◽  
Spectroscopic Studies ◽  
Mononuclear Complex

Mononuclear complex [Fe(3-bpp)2](CF3COO)2 exhibits a thermal (HS + HS) ⇋ (HS + LS) transition at ∼226 K which is not associated with any crystallographic transition.

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