scholarly journals Effect of side-chain amide thionation on turnover of β-lactam substrates by β-lactamases. Further evidence on the question of side-chain hydrogen-bonding in catalysis

1992 ◽  
Vol 286 (3) ◽  
pp. 857-862 ◽  
Author(s):  
R F Pratt ◽  
R Krishnaraj ◽  
H Xu
Keyword(s):  
Hydrogen Bond ◽  
Hydrogen Bonding ◽  
Essential Feature ◽  
Donor Site ◽  
Site Directed Mutagenesis ◽  
Side Chain ◽  
Beta Lactam ◽  
Hydrogen Bond Donor ◽  
Beta Lactamases ◽  
Beta Lactamase Ii

Two side-chain-thionated beta-lactams, a penicillin and a cephalosporin, have been prepared and found to be not significantly poorer as substrates of typical serine (classes A and C) beta-lactamases than are their oxo analogues. This result is interpreted to mean that any hydrogen-bonding site on these enzymes for the beta-lactam side-chain amide carbonyl group must be flexible and is more likely to be a passive rather than active or essential feature of the active site. Previously, data from crystal structures and site-directed mutagenesis had suggested that the side chain of Asn-132 of class-A beta-lactamases, a component of the conserved SDN loop, forms a hydrogen bond with the side-chain carbonyl of the beta-lactam substrate and may provide significant transition-state stabilization during catalysis. The thionocephalosporin was also equally as good as its oxo analogue as a substrate of the class-B beta-lactamase II of Bacillus cereus and not significantly less effective as an inhibitor of the Streptomyces R61 DD-peptidase; a tight hydrogen-bond donor site for the beta-lactam side-chain amide is apparently not present in these enzymes either.

scholarly journals Streptomyces albus G serine β-lactamase. Probing of the catalytic mechanism via molecular modelling of mutant enzymes

1992 ◽  
Vol 282 (1) ◽  
pp. 189-195 ◽  
Author(s):  
J Lamotte-Brasseur ◽  
F Jacob-Dubuisson ◽  
G Dive ◽  
J M Frère ◽  
J M Ghuysen
Keyword(s):  
Hydrogen Bonding ◽  
Active Site ◽  
Catalytic Mechanism ◽  
Site Directed Mutagenesis ◽  
Network Configuration ◽  
Beta Lactam ◽  
Beta Lactamases ◽  
Class A ◽  
Streptomyces Albus ◽  
Hydrogen Bonding Network

In previous studies, several amino acids of the active site of class A beta-lactamases have been modified by site-directed mutagenesis. On the basis of the catalytic mechanism proposed for the Streptomyces albus G beta-lactamase [Lamotte-Brasseur, Dive, Dideberg, Charlier, Frère & Ghuysen (1991) Biochem. J. 279, 213-221], the influence that these mutations exert on the hydrogen-bonding network of the active site has been analysed by molecular mechanics. The results satisfactorily explain the effects of the mutations on the kinetic parameters of the enzyme's activity towards a set of substrates. The present study also shows that, upon binding a properly structured beta-lactam compound, the impaired cavity of a mutant enzyme can readopt a functional hydrogen-bonding-network configuration.

Structure, stability and folding of the α-helix

2001 ◽  
Vol 68 ◽  
pp. 95-110 ◽  
Author(s):  
Andrew J. Doig ◽  
Charles D. Andrew ◽  
Duncan A. E. Cochran ◽  
Eleri Hughes ◽  
Simon Penel ◽  
...  
Keyword(s):  
Hydrogen Bonding ◽  
Hydrophobic Interactions ◽  
Data Bank ◽  
Site Directed Mutagenesis ◽  
Model Systems ◽  
Side Chain ◽  
Structure Stability ◽  
Helical Peptides ◽  
Vast Number ◽  
Α Helix

Pauling first described the α-helix nearly 50 years ago, yet new features of its structure continue to be discovered, using peptide model systems, site-directed mutagenesis, advances in theory, the expansion of the Protein Data Bank and new experimental techniques. Helical peptides in solution form a vast number of structures, including fully helical, fully coiled and partly helical. To interpret peptide results quantitatively it is essential to use a helix/coil model that includes the stabilities of all these conformations. Our models now include terms for helix interiors, capping, side-chain interactions, N-termini and 310-helices. The first three amino acids in a helix (N1, N2 and N3) and the preceding N-cap are unique, as their amide NH groups do not participate in backbone hydrogen bonding. We surveyed their structures in proteins and measured their amino acid preferences. The results are predominantly rationalized by hydrogen bonding to the free NH groups. Stabilizing side-chain-side-chain energies, including hydrophobic interactions, hydrogen bonding and polar/non-polar interactions, were measured accurately in helical peptides. Helices in proteins show a preference for having approximately an integral number of turns so that their N- and C-caps lie on the same side. There are also strong periodic trends in the likelihood of terminating a helix with a Schellman or αL C-cap motif. The kinetics of α-helix folding have been studied with stopped-flow deep ultraviolet circular dichroism using synchrotron radiation as the light source; this gives a far superior signal-to-noise ratio than a conventional instrument. We find that poly(Glu), poly(Lys) and alanine-based peptides fold in milliseconds, with longer peptides showing a transient overshoot in helix content.

scholarly journals Machine learning models for hydrogen bond donor and acceptor strengths using large and diverse training data generated by first-principles interaction free energies

2019 ◽  
Vol 11 (1) ◽  
Author(s):  
Christoph A. Bauer ◽  
Gisbert Schneider ◽  
Andreas H. Göller
Keyword(s):  
Machine Learning ◽  
Hydrogen Bond ◽  
Hydrogen Bonding ◽  
Training Data ◽  
Free Energies ◽  
Hydrogen Bond Donor ◽  
Chemical Application ◽  
Hydrogen Bond Acceptor ◽  
Donor And Acceptor ◽  
Target Values

Abstract We present machine learning (ML) models for hydrogen bond acceptor (HBA) and hydrogen bond donor (HBD) strengths. Quantum chemical (QC) free energies in solution for 1:1 hydrogen-bonded complex formation to the reference molecules 4-fluorophenol and acetone serve as our target values. Our acceptor and donor databases are the largest on record with 4426 and 1036 data points, respectively. After scanning over radial atomic descriptors and ML methods, our final trained HBA and HBD ML models achieve RMSEs of 3.8 kJ mol−1 (acceptors), and 2.3 kJ mol−1 (donors) on experimental test sets, respectively. This performance is comparable with previous models that are trained on experimental hydrogen bonding free energies, indicating that molecular QC data can serve as substitute for experiment. The potential ramifications thereof could lead to a full replacement of wetlab chemistry for HBA/HBD strength determination by QC. As a possible chemical application of our ML models, we highlight our predicted HBA and HBD strengths as possible descriptors in two case studies on trends in intramolecular hydrogen bonding.

Selective encapsulation and extraction of hydrogenphosphate by a hydrogen bond donor tripodal receptor

CrystEngComm ◽  
2020 ◽  
Vol 22 (37) ◽  
pp. 6152-6160
Author(s):  
Sandeep Kumar Dey ◽  
Archana ◽  
Sybil Pereira ◽  
Sarvesh S. Harmalkar ◽  
Shashank N. Mhaldar ◽  
...  
Keyword(s):  
Hydrogen Bond ◽  
Hydrogen Bonding ◽  
Hydrogen Bonds ◽  
Hydrogen Bond Donor ◽  
Tripodal Receptor ◽  
Multiple Hydrogen Bonds

Intramolecular N–H⋯OC hydrogen bonding between the inner amide groups dictates the receptor–anion complementarity in a tripodal receptor towards selective encapsulation of hydrogenphosphate in the outer urea cavity by multiple hydrogen bonds.

Polysulfonylamine, CXXVI [1] Wasserstoffbrücken in kristallinen Onium-dimesylamiden: Ein robustes Achtring-Synthon in Koexistenz mit einem dritten Wasserstoffbrückenmotiv - Cyclodimere, Ketten, supramolekulare Bindungsisomere und ein fünffach verwobenes dreidimensionales (C-H ∙∙∙ O - Netzwerk / Polysulfonylamines, CXXVI [1] Hydrogen Bonding in Crystalline Onium Dimesylamides: A Robust Eight- Membered Ring Synthon in Coexistence with a Third Hydrogen Bonding Motif - Cyclodimers, Chains, Supramolecular Linkage Isomers, and a Quintuply Interwoven Three-Dimensional C - H ∙∙∙ O Network

2000 ◽  
Vol 55 (8) ◽  
pp. 738-752 ◽  
Author(s):  
Oliver Moers ◽  
Karna Wijaya ◽  
Ilona Lange ◽  
Armand Blaschette ◽  
Peter G. Jones
Keyword(s):  
Hydrogen Bond ◽  
Hydrogen Bonding ◽  
Crystal Engineering ◽  
Ion Pairs ◽  
Three Dimensional ◽  
Membered Ring ◽  
Monoclinic Space Group ◽  
Hydrogen Bond Donor ◽  
Linkage Isomers ◽  
Ionic Solids

As an exercise in crystal engineering, low-temperature X-ray structures were determined for six rationally designed ionic solids of general formula BH+(MeSO2)2N−, where BH+ is 2-aminopyridinium (2, monoclinic, space group P21/c, Z = 4), 2-aminopyrimidinium (3, orthorhombic, Pbca, Z = 8), 2-aminothiazolium (4, orthorhombic, Pbcn, Z = 8), 2-amino-6-methylpyridinium (5, solvated with 0.5 H20, monoclinic, C2/c, Z = 8), 2-amino-1,3,4-thiadiazolium (6, triclinic, P1̄, Z = 2), or 2-amino-4,6-dimethylpyrimidinium (7, orthorhombic. Fdd2, Z = 16). The onium cations in question exhibit a trifunctional hydrogen-bond donor sequence H − N (H*)-C (sp2) − N − H , which is complementary to an O − S (sp3)−N fragment of the anion and simultaneously expected to form a third hydrogen bond via the exocyclic N − H* donor. Consequently, all the crystal packings contain cation-anion pairs assembled by an N − H ∙∙∙ N and an N −H ∙∙∙ O hydrogen bond, these substructures being mutually associated through an N − H* ∙∙∙ O bond. For the robust eight-membered ring synthon within the ion pairs [graph set N2 = R22(8), antidromic], two supramolecular isomers were observed: In 2 and 3, N − H ∙∙∙ N originates from the ring NH donor and N − H ∙∙∙ O from the exocyclic amino group, whereas in 4-7 these connectivities are reversed. The third hydrogen bond, N − H*∙∙∙ O , leads either to chains of ion pairs (generated by a 21 transformation in 2-4 or by a glide plane in 5) or to cyclic dimers of ion pairs (Ci symmetric in 6, C2-symmetric in 7). The overall variety of motifs observed in a small number of structures reflects the limits imposed on the prediction of hydrogen bonding patterns. Owing to the excess of potential acceptors over traditional hydrogen-bond donors, several of the structures display prominent non-classical secondary bonding. Thus, the cyclodimeric units of 6 are associated into strands through short antiparallel O ∙∙∙ S(cation) interactions. In the hemihydrate 5, two independent C-H(cation) ∙∙∙ O bonds generate a second antidromic R22(8) pattern, leading to sheets composed of N − H ∙∙∙ N/O connected catemers; the water molecules are alternately sandwiched between and O - H ∙∙∙ O bonded to the sheets to form bilayers, which are cross-linked by a third C − H (cation ) ∙∙∙ O contact. The roof-shaped cyclodimers occurring in 7 occupy the polar C2 axes parallel to z and build up hollow Car− H ∙∙∙ O bonded tetrahedral lattices; in order to fill their large empty cavities, five translationally equivalent lattices mutually interpenetrate.

scholarly journals Site-directed mutagenesis of dicarboxylic acids near the active site of Bacillus cereus 5/B/6 β-lactamase II

1991 ◽  
Vol 276 (2) ◽  
pp. 401-404 ◽  
Author(s):  
H M Lim ◽  
R K Iyer ◽  
J J Pène
Keyword(s):  
Bacillus Cereus ◽  
Aspartic Acid ◽  
Carboxy Group ◽  
Active Site ◽  
Site Directed Mutagenesis ◽  
Directed Mutagenesis ◽  
Beta Lactamase ◽  
Beta Lactam ◽  
Aspartic Acid Residue ◽  
Beta Lactamase Ii

An amino acid residue functioning as a general base has been proposed to assist in the hydrolysis of beta-lactam antibiotics by the zinc-containing Bacillus cereus beta-lactamase II [Bicknell & Waley (1985) Biochemistry 24, 6876-6887]. Oligonucleotide-directed mutagenesis of cloned Bacillus cereus 5/B/6 beta-lactamase II was used in an ‘in vivo’ study to investigate the role of carboxy-group-containing amino acids near the active site of the enzyme. Substitution of asparagine for the wild-type aspartic acid residue at position 81 resulted in fully functional enzyme. An aspartic acid residue at position 90 is essential for beta-lactamase II to confer any detectable ampicillin and cephalosporin C resistance to Escherichia coli. Conversion of Asp90 into Asn90 or Glu90 lead to the synthesis of inactive enzyme, suggesting that the spatial position of the beta-carboxy group of Asp90 is critical for enzyme function.

scholarly journals 4-(3-Bromopropyloxy)-1-hydroxy-9,10-anthraquinone

IUCrData ◽  
2016 ◽  
Vol 1 (5) ◽  
Author(s):  
Natsumi Ohira ◽  
Munenori Takehara ◽  
Yoshinori Inoue ◽  
Chitoshi Kitamura
Keyword(s):  
Hydrogen Bond ◽  
Hydrogen Bonds ◽  
Title Compound ◽  
Ring System ◽  
Side Chain ◽  
Hydrogen Bond Donor ◽  
Torsion Angles ◽  
Compound C ◽  
Benzene Rings ◽  
Ring Motif

In the molecule of the title compound, C17H13BrO4, the anthraquinone ring system is slightly bent, with a dihedral angle of 169.99 (7)° between the planes of the two benzene rings. The side chain (O—C—C—C—Br) has agauche–gaucheconformation, as indicated by the O—C—C—C and C—C—C—Br torsion angles of −66.9 (2) and −65.8 (2)°, respectively. In addition, there is an intramolecular O—H...O hydrogen bond enclosing anS(6) ring motif. The hydrogen-bond donor is bifurcated; in the crystal, a pair of O—H...O hydrogen bonds connects two molecules, forming an inversion dimer with anR22(12) ring motif.

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