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Structures that impact our daily lives

Since the last IUCr Newsletter was published, many structures illustrating aspects of the molecular machinery essential to life have been reported, including the size and shape of the nuclear pore complex, the details of mechanisms of ion transport through membrane channels, mechanism of cell division in bacteria, carbon utilization for survival, molecular details of angiogenesis, nucleosome organization vital to chromatin integrity, evolution of the respiratory chain and synthesis of enzymes.

Some specific recent crystallographic findings with impact on our daily lives include the following.

Macromolecular structure determination of the crystalline complex of phosphatidyl inosital phosphate bound to the surface of the vitamin E transfer protein reveals the nature of the binding, the importance of the binding to vitamin E function and why specific inherited mutations lead to familial vitamin E deficiency [N. Kono et al., Science (2013), 340, 1106, doi: 10.1126/science.1233508].

The structure of a toxic protein from the Salmonella strain responsible for typhoid fever has been found to be a complex of three well defined and separate domains in which two subunits are connected by a single disulfide link [J. Song et al., Nature (2013), 499, 350-352, doi: 10.1038/nature12377]. The structural insights could lead to the design of new antibiotics and vaccines to combat typhoid, which kills 200,000 people worldwide each year.

[3zoj] PDB ID 3zoj.

A high-resolution (0.8 Å) structure of an aquaporin [U. Kosinska et al., Science (2013), 340, 1346, doi: 10.1126/science.1234306] provides details about the exact pathway that water molecules follow through a channel of 6 transmembrane α-helices. The identity of the residue in the channel also explains why OH and H2O+ do not pass through the channel.

Structures of wild type and mutant forms of hemagglutinin from an H5N1 virus bound to avian or human receptor sialic acid analogs reveal a conformational transmission from birds to humans [W. Zhang et al., Science (2013), 340, 1463].

[4lrh] PDB ID 4lrh.

The structures of the folate receptor (a major target for cancer chemotherapy) with folic acid in the active site [K. Melcher, Nature (2013), 500, 486-489, doi: 10.1038/nature12327] will foster design of better anticancer agents.

The structure of the first member of class B G-protein-coupled receptors, corticotrophin releasing factor receptor 1, revealed features useful for the development of new drugs to combat diseases of the brain and of metabolism [K. Hollenstein et al., Nature (2013), 499, 438].

[3w9h] PDB ID 3w9h.

Because E. flux transporters are responsible for drug resistance in Gram-negative bacteria, the recent determination of a complex of a selective inhibitor bound to one of these transporters [R. Nakashima et al., Nature (2013), 500, 102-106, doi: 10.1038/nature12300] reveals the site of binding and can be used to design potential and selective blockers of drug resistance.

The cause of a debilitating side effect of a sulfonamide antibiotic that has been used for over 50 years was recently determined to result from binding of the antibiotic to an enzyme essential to the production of neurotransmitters. The crystal structure of the complex of sulfamerthazine to the enzyme (sepiaperin reductase) should lead to redesign of antibiotic derivatives with reduced neurotransmitter inhibition. [K. Johnsson, Science (2013), 340, 987-991, doi: 10:1126/scoemce1232972.]

[4jha] PDB ID 4jha.

Respiratory syncytial virus (RSV) infects nearly all children by 3 years of age and is a leading cause of infant mortality. The crystal structure of the complex of an antibody and the glycoprotein F of RSV reveals the mechanism of binding and will support design of improved vaccine antigens. [J. S. McLellan et al., Science (2013), 340, 1113-1117, doi: 10.1126/science.1234914.]

The structures of a corona virus responsible for severe pulmonary disease in humans and its complex with the cellular receptor [G. Lu et al., Nature (2013), 500, 227-231, doi: 10.1038/nature12328] reveal a common core in the structure of coronoviruses but high variation in the external binding motifs region responsible for virus-specific pathogenesis and insight into pathogen-targeted therapy.

Comparison of the crystal structures of wild type and mutant forms of an inhibitory receptor on macrophages complexed with CD47 (an antiphagocytic signal) provides molecular details of a synergistically increased phagocytosis in vitro and enhanced antitumor response in vivo that may be a universal method of augmenting the efficacy of therapeutic anticancer antibiotics. [K. Weiskopf et al., Science (2013), 341, 88-89, doi: 10.1126/science.1238856.]

[4kzx] PDB ID 4kzx.

The structures of three complexes of the small ribosomal subunit define three steps in mammalian translation and initiation and reveal the dynamics of the interaction in the P site of the ribosome [I. B. Lomaken, Nature (2013), 500, 307-311, doi: 10.1038/nature12355].

Many predatory bacteria synthesize a large spike-shaped multi-molecular machine with which they inject toxins into other species and destroy them. A recent structure determination reveals the details of piercing tips of the spike [M. Shneider et al., Nature (2013), 500, 350-353, doi: 10.1038/nature12453].

[895701] CSD No. 895701.

Just as Dorothy Hodgkin determined the correct structure of penicillin in the 1930s with a single-crystal structure determination, an acrimonious debate over the actual structure of the 2-norbornyl cation has been resolved by X-ray crystallographic demonstration that the carbonium ion is a bridged structure with 'non-classical' geometry [F. Scholz, Science (2013), 341, 62, doi: 10.1126/science.1238849].

The computationally designed and crystallographically verified structure of a multi metal ion oxide, with properties of a solid oxide fuel cell cathode, was reported by M. Dyer et al. [Science (2013), 340, 847-852, doi: 10.1126/science.1226558]. The oxide consists of specific composition of Y, Ba, Ca, Fe and Cu that has a 60 Å cell side and 148 atoms in the unit cell.

[918417] CSD No. 918417.

Recent crystallographic structures of new materials with economic potential include a cyclodextrin offering a 'greener' method for gold recovery [J. F. Stoddart, Nat. Commun. (2013), 4, doi: 10.1038/ncomms2891], mesoporous single crystals of semiconducting titanium dioxide [E. J. W. Crossland et al., Nature (2013), 495, 215-219, doi: 10.1038/nature11936], a metal-organic framework that enhances fuel efficiency [J. R. Long et al., Science (2013), 340, 960-964, doi: 10.1126/science.1234071], and a complex binary solid having reproducible electronic and magnetic properties prepared by combining fullerenes with a metal triethyl phosphate cluster [X. Roy et al., Science (2013), 341, 157-160, doi: 10.1126/science.1236259].

[937386] CSD No. 937386.

A trinuclear titanium polyhydride cluster that cleaves and functionalizes N2, forming N-H bonds essential to converting abundant N2 molecules in the air into a chemically usable form essential to life, has been prepared. Single crystals reveal the long-sought mechanism [T. Shima et al., Science (2013), 340, 1549-1552, doi: 10.1126/science.1238663].

In July 2013, survey articles highlighted proton conduction in metal-organic frameworks (MOFs), and van der Waals heterostructures constructed of two-dimensional atomic crystals appeared in Science (2013, 341, 354, doi: 10.1126/science.1239872) and Nature (2013, 499, 419-425, doi: 10.1038/nature12385), respectively. Crystallographic studies continue to reveal the structures of modern materials that are responsible for unusual properties and phenomena.