scholarly journals Modeling of cytochrome P450 (Cyt P450, CYP) channels

2011 ◽  
Vol 25 (2) ◽  
pp. 63-87 ◽  
Author(s):  
Christopher K. Jankowski ◽  
Julien B. Chiasson ◽  
Étienne Dako ◽  
Kathy Doucet ◽  
Marc E. Surette ◽  
...  
Keyword(s):  
Cytochrome P450 ◽  
Direct Method ◽  
Outer Side ◽  
X Ray ◽  
X Ray Crystallography ◽  
New Methods ◽  
Curved Channels ◽  
Modeling Techniques ◽  
On Line ◽  
Structure Of Proteins

The precise location of a substrate in cytochrome P450 (CYP) governs the orientation of the oxidation position. Such information is generally obtained from biochemical data, but modeling approaches have also been used to explain these locations. We used X-ray data and modeling techniques to distinguish between the series of putative linear or curved channels which lead the substrate from the outer side of the protein to the inner, and then into the heme pocket; these techniques were also used to identify the largest such channels. Two new methods for precisely determining the 3-D structure of proteins using X-ray crystallography were proposed in order to identify these channels: first, the use of both straight and curved channels, and second, the sphere method. These data are compared with Poulos channels, and with Caver (or Mol on line) modeling methodologies. Our methods were developed from studies of the interaction between cytochrome P450CAM(CYP101) fromPseudomonas putida(as expressed inEscherichia coli) and the indolic base β-carboline. Apart from the identification of potential access channels leading to the heme-containing active site, a new explanation was advanced for the substrate's hydroxylation position. The sphere method seems to have potential to become a general and direct method for prediction of substrate access channels from reduced- or low-resolution crystallographic data.

Structural and vibrational studies of 1,1,3,3-tetracyanopropane and 2,2,4,4,6-pentacyanocyclohexenamine

1987 ◽  
Vol 65 (2) ◽  
pp. 261-270 ◽  
Author(s):  
R. A. Bell ◽  
B. E. Brown ◽  
M. Duarte ◽  
H. E. Howard-Lock ◽  
C. J. L. Lock
Keyword(s):  
Unit Cell ◽  
Orthorhombic Space Group ◽  
X Ray ◽  
X Ray Crystallography ◽  
New Methods ◽  
Cell Dimensions ◽  
Cell Data ◽  
Unit Cell Data ◽  
Monoclinic Cell ◽  
C Nmr

1,1,3,3-Tetracyanopropane, 1, was prepared in low yields by a literature method with 2,2,4,4,6-pentacyanocyclohexenamine, 2, as a major by-product. The products were examined by X-ray crystallography. 1 has an orthorhombic space group, Pbcn (No. 60) with cell dimensions, a = 7.158(2), b = 10.510(3), c = 9.733(2) Å and has four formula units in the unit cell. 2 has a monoclinic cell, P21/c (No. 14) with cell dimensions a = 14.368(3), b = 6.626(1), c = 12.300(2) Å, β = 115.60(1)° and has 4 formula units in the unit cell. Data were collected with use of MoKα radiation and a Nicolet P3 diffractometer. The crystal structures were determined by standard methods and refined to Rw = 0.037 (1) and Rw = 0.040 (2) on the basis of 782 and 2108 unique reflections. Bond lengths and angles in the two compounds are normal. 2 has what has been considered to be the less likely tautomeric structure. Both compounds were examined by 1H, 13C nmr, vibrational spectroscopy, and mass spectroscopy. For 2 there was no evidence of the alternative tautomeric structure. New methods were developed for the preparation of both compounds and the mechanism of the original reaction rationalized.

Introduction

1986 ◽  
Vol 317 (1540) ◽  
pp. 293-294 ◽  
Keyword(s):  
Direct Method ◽  
Hydrolytic Enzyme ◽  
Hydrolytic Enzymes ◽  
Three Dimensional ◽  
X Ray ◽  
Enzyme Active Site ◽  
X Ray Crystallography ◽  
Protein Molecules ◽  
Biological Catalysis ◽  
The 1960S

Our understanding of the function of protein molecules was revolutionized in the 1960s by the use of X-ray crystallography to give a three-dimensional picture of their structures at atomic resolution. The structure of myoglobin was rapidly followed by the structure of several hydrolytic enzymes such as lysozyme, carboxypeptidase, ribonuclease, chymotrypsin, and subtilisin; and, not long after, by the much more complicated structure of haemoglobin, composed of four myoglobin-like molecules interacting with each other. The first hydrolytic enzyme structures showed us how enzymes perform biological catalysis by immobilizing their substrates at the enzyme active site, and gave us definite ideas about the specific functions of different parts of the protein molecules. These ideas had to be treated as hypotheses, because there was no direct method to check them. A few particular points could be proved by cunning but tedious experiments.

Electron Donor-Acceptor Compounds. Synthesis and Structure of 5-(1,4-Benzoquinone-2-yl)-10,15,20-trialkylporphyrins

1998 ◽  
Vol 53 (9) ◽  
pp. 1021-1030 ◽  
Author(s):  
Steffen Runge ◽  
Mathias O. Senge
Keyword(s):  
Crystal Structure ◽  
Structure Analysis ◽  
Supramolecular Structure ◽  
Crystal Structure Analysis ◽  
Free Base ◽  
X Ray ◽  
X Ray Crystallography ◽  
New Methods ◽  
Polymeric Chains ◽  
Donor Acceptor

Abstract A series of 5-(benzoquinone)-10,15,20-trialkylporphyrins was synthesized via cross condensation of the respective aldehydes, 2,5-dimethoxybenzaldehyde and pyrrole followed by demethylation with BBr3 and oxidation with PbO2. This method worked reasonably well for compounds bearing the benzoquinone substituent and butyl, isopropyl, 1 -methylpropyl and 2-ethylpropyl residues (2a-d). The free base porphyrin quinones were converted into the zinc(II) complexes (3a-d) all of which showed remarkable stability for porphyrin quinones. The zinc(II) complex 3c bearing isopropyl residues was investigated by X-ray crystallography and showed a supramolecular structure consisting of polymeric chains facilitated by coordina­tion of a benzoquinone oxygen to a neighboring zinc(II) center. Attempts to synthesize a 5-(benzoquinone)-10,15,20-tris(terr-butylporphyrin) resulted in the formation of a yellow porphomethene (4), which could not be oxidized further. A crystal structure analysis of 4, the first for a free base porphomethene, shows an extremely twisted conformation with syn-orientation of the three tert-butyl groups. The results indicate that new methods will have to be developed for the synthesis of nonplanar porphyrin quinones.

scholarly journals Reciprocalspaceship: A Python Library for Crystallographic Data Analysis

2021 ◽  
Author(s):  
Jack B. Greisman ◽  
Kevin M. Dalton ◽  
Doeke R. Hekstra
Keyword(s):  
Data Analysis ◽  
Exploratory Data Analysis ◽  
X Ray ◽  
X Ray Crystallography ◽  
New Methods ◽  
Reflection Data ◽  
Software Packages ◽  
Automated Processing ◽  
Exploratory Data ◽  
Closed Source

AbstractX-ray crystallography is an invaluable technique for studying the atomic structure of macromolecules. Much of crystallography’s success is due to the software packages developed to enable the automated processing of diffraction data. However, the analysis of unconventional diffraction experiments can still pose significant challenges—many existing programs are closed-source, sparsely documented, or are challenging to integrate with modern libraries for scientific computing and machine learning. Here we describe reciprocalspaceship, a Python library for exploring reciprocal space. It provides a tabular representation for reflection data from diffraction experiments that extends the widely-used pandas library with built-in methods for handling space group, unit cell, and symmetry-based operations. As we illustrate, this library facilitates new modes of exploratory data analysis while supporting the prototyping, development, and release of new methods.

Lawrence Bragg and Linus Pauling: Comparisons and Rivalries

2020 ◽  
pp. 135-149
Author(s):  
John Meurig Thomas
Keyword(s):  
Twentieth Century ◽  
Protein Structures ◽  
Alpha Helix ◽  
Nobel Laureate ◽  
Linus Pauling ◽  
X Ray ◽  
X Ray Crystallography ◽  
The World ◽  
Structure Of Proteins

W. L. Bragg and L. C. Pauling were among the most famous scientists in the world for much of the twentieth century. Each was a Nobel Laureate, and each was admired, not only for their fundamental achievements in X-ray crystallography, but also as exemplary popularizers of science. In the fields of mineralogy (especially the structure of silicates) and protein structures, their interests overlapped. They admired their respective technical virtuosities, but there was deep-seated rivalry between them. It irked Bragg that Pauling had formulated simple stereochemical rules to account for the multiplicity of structures exhibited by vast numbers of silicates, and also that Pauling had proposed the existence of the alpha-helix and pleated sheets as motifs in the structure of proteins like keratin. The details of their rivalry, bordering on envy, is described through specific examples.

scholarly journals Synthesis, X-ray crystal structure, Hirshfeld surface analysis, and molecular docking studies of DMSO/H2O solvate of 5-chlorospiro[indoline-3,7'-pyrano[3,2-c:5,6-c']dichromene]-2,6',8'-trione

2021 ◽  
Vol 12 (4) ◽  
pp. 382-388
Author(s):  
Varun Sharma ◽  
Bubun Banerjee ◽  
Aditi Sharma ◽  
Vivek Kumar Gupta
Keyword(s):  
Crystal Structure ◽  
Molecular Docking ◽  
Direct Method ◽  
Docking Studies ◽  
One Pot ◽  
X Ray ◽  
Molecular Docking Studies ◽  
X Ray Crystallography ◽  
Three Component Reaction ◽  
Inhibition Property

The title compound, 5-chlorospiro[indoline-3,7'-pyrano[3,2-c:5,6-c']dichromene]-2,6',8'-trione was synthesized via one-pot pseudo three-component reaction between one equivalent of 5-chloroisatin and two equivalents of 4-hydroxycoumarin using mandelic acid as catalyst in aqueous ethanol at 110 °C. The synthesized compound was characterized by FT-IR, 1H NMR, and HRMS techniques. Single crystals were grown for crystal structure determination by using single X-ray crystallography technique. It was found that the crystals are triclinic with space group P-1 and Z = 1. The crystal structure was solved by direct method and refined by full-matrix least-squares procedures to a final R-value of 0.0688 for 6738 observed reflections. The crystal structure was stabilized by elaborate system of O-H···O, N-H···O, and C-H···O interactions with the formation of supramolecular structures. 3D Hirshfeld surfaces and allied 2D fingerprint plots were analyzed for molecular interactions. Molecular docking studies have been performed to get insights into the inhibition property of this molecule for Human topoisomerase IIα.

scholarly journals The Structure of Human Microsomal Cytochrome P450 3A4 Determined by X-ray Crystallography to 2.05-Å Resolution: Fig. 1.

2004 ◽  
Vol 279 (37) ◽  
pp. 38091-38094 ◽  
Author(s):  
Jason K. Yano ◽  
Michael R. Wester ◽  
Guillaume A. Schoch ◽  
Keith J. Griffin ◽  
C. David Stout ◽  
...  
Keyword(s):  
Cytochrome P450 ◽  
Cytochrome P450 3A4 ◽  
Microsomal Cytochrome ◽  
X Ray ◽  
X Ray Crystallography ◽  
Microsomal Cytochrome P450

Address of the President Lord Todd, O. M. at the Anniversary Meeting, 3 0 November 1979

1980 ◽  
Vol 369 (1738) ◽  
pp. 295-306 ◽  
Keyword(s):  
Three Dimensional ◽  
Dimensional Structure ◽  
Detailed Understanding ◽  
X Ray ◽  
X Ray Crystallography ◽  
Pathological Conditions ◽  
Physiological Properties ◽  
The Subject ◽  
Investigative Techniques ◽  
Structure Of Proteins

The Copley Medal is awarded to Dr M. F. Perutz, C. H., C. B. E., F. R. S., in recognition of his distinguished contributions to molecular biology through his studies of the structure and biological activity of haemoglobin, the oxygen-carrying component of the blood, and his leadership in the development of the subject. Dr Perutz’s studies of haemoglobin have led to a detailed understanding of its physiological properties in terms of its structure and the chemical environment in which it operates. His work has also provided evidence for the genetic control of protein synthesis and has led to the first detailed understanding of the molecular basis for particular pathological conditions. In his research, Dr Perutz has used a large number of investigative techniques, including X-ray crystallography, which in 1953 he first showed could be used to determine the three-dimensional structure of proteins and which has since been used to determine the structure of many proteins and nucleic acids.

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