From Penicillin to the Ribosome: Revolutions in the Determination and Use of Molecular Structure in Chemistry and Biology

2004 ◽  
Vol 57 (9) ◽  
pp. 829 ◽  
Author(s):  
Edward N. Baker
Keyword(s):  
Biological Sciences ◽  
Molecular Structure ◽  
Structural Genomics ◽  
Structure Determination ◽  
Biological Function ◽  
Structural Information ◽  
Structure Based Drug Design ◽  
X Ray ◽  
X Ray Crystallography

A revolution in structural analysis is in progress in the biological sciences that parallels a similar revolution that took place in chemistry 40–50 years ago. This has major implications for chemistry, offering exciting opportunities at the interface between chemistry and biology. The advances are driven by the value of structural information in biology, for understanding biological function, and for applications in structure-based drug design and structural genomics. Two directions are apparent: towards technically challenging biological structures and assemblies, typified by the potassium channel and the ribosome; and towards high-throughput structure determination of many, smaller, proteins, as in structural genomics. In this review, the advances in molecular biology and in structure determination by X-ray crystallography that make these developments possible are discussed, together with appropriate examples.

scholarly journals Structure determination of GPCRs: cryo-EM compared with X-ray crystallography

2021 ◽  
Author(s):  
Javier García-Nafría ◽  
Christopher G. Tate
Keyword(s):  
Structural Biology ◽  
Structure Determination ◽  
Drug Targets ◽  
Cellular Systems ◽  
Single Family ◽  
Structure Based Drug Design ◽  
X Ray ◽  
Surface Receptors ◽  
X Ray Crystallography

G protein-coupled receptors (GPCRs) are the largest single family of cell surface receptors encoded by the human genome and they play pivotal roles in co-ordinating cellular systems throughout the human body, making them ideal drug targets. Structural biology has played a key role in defining how receptors are activated and signal through G proteins and β-arrestins. The application of structure-based drug design (SBDD) is now yielding novel compounds targeting GPCRs. There is thus significant interest from both academia and the pharmaceutical industry in the structural biology of GPCRs as currently only about one quarter of human non-odorant receptors have had their structure determined. Initially, all the structures were determined by X-ray crystallography, but recent advances in electron cryo-microscopy (cryo-EM) now make GPCRs tractable targets for single-particle cryo-EM with comparable resolution to X-ray crystallography. So far this year, 78% of the 99 GPCR structures deposited in the PDB (Jan–Jul 2021) were determined by cryo-EM. Cryo-EM has also opened up new possibilities in GPCR structural biology, such as determining structures of GPCRs embedded in a lipid nanodisc and multiple GPCR conformations from a single preparation. However, X-ray crystallography still has a number of advantages, particularly in the speed of determining many structures of the same receptor bound to different ligands, an essential prerequisite for effective SBDD. We will discuss the relative merits of cryo-EM and X-ray crystallography for the structure determination of GPCRs and the future potential of both techniques.

4,4′-Bithiazoles as Ligands: Crystal and Molecular Structure of bis(O,O′-Nitrato)(2,2′-diphenyl-4,4′-bithiazole)copper(II) (Two Polymorphs)

2003 ◽  
Vol 56 (9) ◽  
pp. 949 ◽  
Author(s):  
S. Ali Asghar Torabi ◽  
Fahimeh Jamali ◽  
George A. Koutsantonis ◽  
Ali Morsali ◽  
Brian W. Skelton ◽  
...  
Keyword(s):  
Molecular Structure ◽  
Low Temperature ◽  
Molecular Complex ◽  
Structure Determination ◽  
Crystal And Molecular Structure ◽  
Plane Angle ◽  
Asymmetric Unit ◽  
X Ray ◽  
Crystallographic Symmetry

A low-temperature single-crystal X-ray structure determination of the 1 : 1 adduct of copper(II) nitrate with 2,2′-diphenyl-4,4′-bithiazole (L) shows it to be a molecular complex with L behaving as a symmetrical N,N′ chelate, and the nitrate groups as unsymmetrical O,O′ chelates: [LCu(O2NO)2]. Two polymorphs, both monoclinic P21/c, have been obtained from acetonitrile (‘α’) and methanol (‘β’), respectively, with one molecule, devoid of crystallographic symmetry, in the asymmetric unit of each structure. The copper environments are distorted planar four-coordinate, cis-N2CuO2 (Cu–N 2.011(1), 1.973(1), Cu–O 1.995(1), 1.962(1) Å), ‘in-plane’ angle sum Σ 369.5°, with longer trans, axial contacts (Cu–O 2.455(1), 2.458(2) Å) for the α-form; respective values are 1.995(5), 1.991(4), 1.997(4), 1.973(3) Å, 360.4°, 2.500(4), and 2.396(4) Å for the β-form.

scholarly journals Structure Determination of Membrane Proteins Using X-Ray Crystallography

2021 ◽  
pp. 101-136
Author(s):  
Evan Billings ◽  
Karl Lundquist ◽  
Claire Overly ◽  
Karthik Srinivasan ◽  
Nicholas Noinaj
Keyword(s):  
Membrane Proteins ◽  
Structure Determination ◽  
X Ray ◽  
X Ray Crystallography

The structure determination of a new cembranolide diterpene from the soft coral Lobophytum cristigalli (Coelenterata, Octocorallia, Alcyonacea)

1984 ◽  
Vol 37 (3) ◽  
pp. 545 ◽  
Author(s):  
BF Bowden ◽  
JC Coll ◽  
MSL de Costa ◽  
MF Mackay ◽  
M Mahendran ◽  
...  
Keyword(s):  
Sri Lanka ◽  
Structure Determination ◽  
Soft Coral ◽  
X Ray ◽  
X Ray Crystallography

A specimen of Lobophytum cristigalli collected in Sri Lanka afforded two cembranolide diterpenes (7E,11E,1R,2S,3R,4R,14S)-14-acetoxy-3,4-epoxycembra-7,11,15-trien-17,2-olide (6)* and the corresponding alcohol (7). Their structures were deduced spectroscopically and detailed stereochemistry of (6) was determined by X-ray crystallography.

scholarly journals Structure determination of a human virus by the combination of cryo-EM and X-ray crystallography

2016 ◽  
Vol 2 (2-4) ◽  
pp. 55-68 ◽  
Author(s):  
Zheng Liu ◽  
Tom S. Y. Guu ◽  
Jianhao Cao ◽  
Yinyin Li ◽  
Lingpeng Cheng ◽  
...  
Keyword(s):  
Structure Determination ◽  
Human Virus ◽  
X Ray ◽  
X Ray Crystallography

N,N′-Dialkyl-4-Aryl-3,4-Dihydropyrimidinones and Thiones: Ceric Ammonium Nitrate Catalyzed Synthesis and Molecular Structure Determination by X-ray Crystallography

2016 ◽  
Vol 54 (2) ◽  
pp. 1486-1491 ◽  
Author(s):  
Chingrishon Kathing ◽  
Sushil Kumar ◽  
Shokip Tumtin ◽  
Nongthombam Geetmani Singh ◽  
Jims World Star Rani ◽  
...  
Keyword(s):  
Molecular Structure ◽  
Ammonium Nitrate ◽  
Structure Determination ◽  
Ceric Ammonium Nitrate ◽  
X Ray ◽  
X Ray Crystallography
Sign in / Sign up

Export Citation Format

Share Document