scholarly journals Using iterative fragment assembly and progressive sequence truncation to facilitate phasing and crystal structure determination of distantly related proteins

2016 ◽  
Vol 72 (5) ◽  
pp. 616-628 ◽  
Author(s):  
Yan Wang ◽  
Jouko Virtanen ◽  
Zhidong Xue ◽  
John J. G. Tesmer ◽  
Yang Zhang
Keyword(s):  
Success Rate ◽  
Structure Determination ◽  
Protein Targets ◽  
Search Models ◽  
X Ray Crystallography ◽  
Structure Genomics ◽  
Related Proteins ◽  
Structure Assembly ◽  
Sequence Truncation

Molecular replacement (MR) often requires templates with high homology to solve the phase problem in X-ray crystallography.I-TASSER-MRhas been developed to test whether the success rate for structure determination of distant-homology proteins could be improved by a combination of iterative fragmental structure-assembly simulations with progressive sequence truncation designed to trim regions with high variation. The pipeline was tested on two independent protein sets consisting of 61 proteins from CASP8 and 100 high-resolution proteins from the PDB. After excluding homologous templates,I-TASSERgenerated full-length models with an average TM-score of 0.773, which is 12% higher than the best threading templates. Using these as search models,I-TASSER-MRfound correct MR solutions for 95 of 161 targets as judged by having a TFZ of >8 or with the final structure closer to the native than the initial search models. The success rate was 16% higher than when using the best threading templates.I-TASSER-MRwas also applied to 14 protein targets from structure genomics centers. Seven of these were successfully solved byI-TASSER-MR. These results confirm that advanced structure assembly and progressive structural editing can significantly improve the success rate of MR for targets with distant homology to proteins of known structure.

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.

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

Studies of Australian Soft Corals .XXXVII. The Structure Determination of 2 Cembranolide Diterpenes From Soft Corals of the Genus Efflatounaria (Coelenterata, Octocorallia, Alcyonacea)

1986 ◽  
Vol 39 (1) ◽  
pp. 123 ◽  
Author(s):  
BF Bowden ◽  
JC Coll ◽  
LM Engelhardt ◽  
GV Meehan ◽  
GG Pegg ◽  
...  
Keyword(s):  
Structure Determination ◽  
Soft Coral ◽  
Soft Corals ◽  
X Ray ◽  
X Ray Crystallography ◽  
Coral Genus ◽  
Relative Stereochemistry ◽  
Chemical Correlation ◽  
Absolute Stereochemistry

Two isomeric 7,8-epoxycembra-3,11,15-trien-16,2-olides have been isolated from different species of the soft coral genus Efflatounaria. The structure of each was deduced spectroscopically , and the relative stereochemistry of one was determined by X-ray crystallography. The absolute stereochemistry of each cembranolide was obtained by chemical correlation with known compounds.

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