X-ray crystallography marries spectroscopy to unveil structure and function of biological macromolecules

2011 ◽  
Vol 1814 (6) ◽  
pp. 731-733 ◽  
Author(s):  
A.R. Pearson ◽  
Andrea Mozzarelli
Keyword(s):  
Structure And Function ◽  
Biological Macromolecules ◽  
X Ray ◽  
X Ray Crystallography ◽  
And Function

scholarly journals General discussion summary

2002 ◽  
Vol 357 (1426) ◽  
pp. 1419-1420 ◽  
Keyword(s):  
Water Splitting ◽  
Molecular Mechanisms ◽  
Structure And Function ◽  
X Ray ◽  
X Ray Crystallography ◽  
And Function ◽  
Splitting Process

This general discussion was chaired by A. W. Rutherford ( Service de Bioénergétique, Saclay, France ) and revolved around two major topics: (i) the implications of X–ray crystallography on the relationships between structure and function; (ii) the molecular mechanisms of the water–splitting process.

Structure and Function Studies of Factor XIIIa by x-ray Crystallography

1996 ◽  
Vol 22 (05) ◽  
pp. 377-384 ◽  
Author(s):  
Vivien Yee ◽  
Isolde Le Trong ◽  
Paul Bishop ◽  
Lars Pedersen ◽  
Ronald Stenkamp ◽  
...  
Keyword(s):  
Structure And Function ◽  
Factor Xiiia ◽  
X Ray ◽  
X Ray Crystallography ◽  
And Function

Studies on the Structure and Function of Ribosomes by Combined Use of Chemical Probing and X-Ray Crystallography

The Ribosome ◽  
2014 ◽  
pp. 127-150
Author(s):  
Harry F. Noller ◽  
Jamie Cate ◽  
Anne Dallas ◽  
Gloria Culver ◽  
Thomas N. Earnest ◽  
...  
Keyword(s):  
Structure And Function ◽  
X Ray ◽  
X Ray Crystallography ◽  
Chemical Probing ◽  
Combined Use ◽  
And Function

The Structure and Function of Estrogens. XI. Synthesis of (±)-7(8→11α)abeo-Estradiol and Its 9,11-Didehydro Derivative

1992 ◽  
Vol 45 (1) ◽  
pp. 71 ◽  
Author(s):  
DJ Collins ◽  
GD Fallon ◽  
CE Skene
Keyword(s):  
Conjugate Addition ◽  
Structure And Function ◽  
Reductive Cleavage ◽  
X Ray ◽  
X Ray Crystallography ◽  
Cyclopropyl Ketone ◽  
And Function

Two approaches to the synthesis of (�)-7(8→11α)abeo-estra-1,3,5(10)-triene-3,17 β- diol (2a) from (�)-1 β-t-butoxy-7a β-methy1-2,3,3a α,6,7,7a-hexahydro-1H-inden-5(4H)-one (11) were studied. A pathway involving 6-alkylation of (11) with 2-(3′-methoxyphenyl)ethyl halides or sulfonate esters was unsuccessful, but conjugate addition of 3-methoxybenzyl nucleophiles with (�)-1β-t-butoxy-7a β-methyl-6-methylene-2,3,3a,6,7,7a-hexahydro-1H-inden-5(4H)-one (18), prepared from (11), led to ( �)-1β-t-butoxy-6 α-[2′-(3″-methoxyphenyl)ethy1]-7a β α,6,7,7a-hexahydro-1H-inden-5(4H-one (10a). Acid-catalysed cyclization of (10a) afforded (�)-17β-t-butoxy-3-methoxy-7(8 →11)abeo-estra-l,3,5(10),9(11)-tetraene (29) which upon lithium/ammonia reduction in the presence of diphenylmethane gave ( �)-17 β- t-butoxy-3-methoxy-7(8 →11α)abeo-estra,1,3,5(10)- triene (31). Deprotection of (31) and (29) afforded (�)-7(8 →11 α)abeo-estra-1,3,5(10)-triene-3,17 β- diol (2a) and (�)-7(8 →1l)abeo-estra-1,3,5(10),9(11)-tetraene-3,17β-diol (32), respectively. Alternatively, reaction of (�)-1β-t-butoxy-7a β-methyl-6-methylene-2,3,3a α,6,7,7a-hexahydro-1H-inden-5(4H)-one (18) with 3-methoxybenzyl phenyl sulfoxide (23a) gave (1RS,3′SR,2RS,-3a′SR,7a′SR)-3′-t-butoxy-2-(3″-methoxyphenyl)-3a′-methyl-2′,3′,3a′,4′7′,7a′-hexahydrospiro- [cyclopropane-1,5′-[5H]inden ]-6′(1′H)-one (26), reductive cleavage of which with lithium/ammonia afforded (10a). The relative stereochemistries of (31) and of the spiro cyclopropyl ketone intermediate (26) were established unambiguously by X-ray crystallography.

scholarly journals Cryo-EM studies of the structure and dynamics of vacuolar-type ATPases

2016 ◽  
Vol 2 (7) ◽  
pp. e1600725 ◽  
Author(s):  
Mohammad T. Mazhab-Jafari ◽  
John L. Rubinstein
Keyword(s):  
Nmr Spectroscopy ◽  
Structure And Function ◽  
Conformational Heterogeneity ◽  
X Ray ◽  
X Ray Crystallography ◽  
Adenosine Triphosphatases ◽  
Different Types ◽  
Ion Gradient ◽  
And Function ◽  
Hydrolysis Of

Electron cryomicroscopy (cryo-EM) has significantly advanced our understanding of molecular structure in biology. Recent innovations in both hardware and software have made cryo-EM a viable alternative for targets that are not amenable to x-ray crystallography or nuclear magnetic resonance (NMR) spectroscopy. Cryo-EM has even become the method of choice in some situations where x-ray crystallography and NMR spectroscopy are possible but where cryo-EM can determine structures at higher resolution or with less time or effort. Rotary adenosine triphosphatases (ATPases) are crucial to the maintenance of cellular homeostasis. These enzymes couple the synthesis or hydrolysis of adenosine triphosphate to the use or production of a transmembrane electrochemical ion gradient, respectively. However, the membrane-embedded nature and conformational heterogeneity of intact rotary ATPases have prevented their high-resolution structural analysis to date. Recent application of cryo-EM methods to the different types of rotary ATPase has led to sudden advances in understanding the structure and function of these enzymes, revealing significant conformational heterogeneity and characteristic transmembrane α helices that are highly tilted with respect to the membrane. In this Review, we will discuss what has been learned recently about rotary ATPase structure and function, with a particular focus on the vacuolar-type ATPases.

scholarly journals Structure and function of L-threonine-3-dehydrogenase from the parasitic protozoan Trypanosoma brucei revealed by X-ray crystallography and geometric simulations

2018 ◽  
Vol 74 (9) ◽  
pp. 861-876 ◽  
Author(s):  
Eyram Adjogatse ◽  
Peter Erskine ◽  
Stephen A. Wells ◽  
John M. Kelly ◽  
Jonathan D. Wilden ◽  
...  
Keyword(s):  
Drug Targets ◽  
Neglected Tropical Diseases ◽  
Three Dimensional ◽  
Initial Step ◽  
Structure And Function ◽  
Dimensional Structure ◽  
X Ray ◽  
X Ray Crystallography ◽  
Key Enzyme ◽  
And Function

Two of the world's most neglected tropical diseases, human African trypanosomiasis (HAT) and Chagas disease, are caused by protozoan parasites of the genus Trypanosoma. These organisms possess specialized metabolic pathways, frequently distinct from those in humans, which have potential to be exploited as novel drug targets. This study elucidates the structure and function of L-threonine-3-dehydrogenase (TDH) from T. brucei, the causative pathogen of HAT. TDH is a key enzyme in the metabolism of L-threonine, and an inhibitor of TDH has been shown to have trypanocidal activity in the procyclic form of T. brucei. TDH is a nonfunctional pseudogene in humans, suggesting that it may be possible to rationally design safe and specific therapies for trypanosomiasis by targeting this parasite enzyme. As an initial step, the TDH gene from T. brucei was expressed and the three-dimensional structure of the enzyme was solved by X-ray crystallography. In multiple crystallographic structures, T. brucei TDH is revealed to be a dimeric short-chain dehydrogenase that displays a considerable degree of conformational variation in its ligand-binding regions. Geometric simulations of the structure have provided insight into the dynamic behaviour of this enzyme. Furthermore, structures of TDH bound to its natural substrates and known inhibitors have been determined, giving an indication of the mechanism of catalysis of the enzyme. Collectively, these results provide vital details for future drug design to target TDH or related enzymes.

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