Infrared and fluorescence assessment of the hydration status of the tryptophan gate in the influenza A M2 proton channel
Literature Information
Beatrice N. Markiewicz, Thomas Lemmin, Wenkai Zhang, Ismail A. Ahmed, Hyunil Jo, Giacomo Fiorin, William F. DeGrado
The M2 proton channel of the influenza A virus has been the subject of extensive studies because of its critical role in viral replication. As such, we now know a great deal about its mechanism of action, especially how it selects and conducts protons in an asymmetric fashion. The conductance of this channel is tuned to conduct protons at a relatively low biologically useful rate, which allows acidification of the viral interior of a virus entrapped within an endosome, but not so great as to cause toxicity to the infected host cell prior to packaging of the virus. The dynamic, structural and chemical features that give rise to this tuning are not fully understood. Herein, we use a tryptophan (Trp) analog, 5-cyanotryptophan, and various methods, including linear and nonlinear infrared spectroscopies, static and time-resolved fluorescence techniques, and molecular dynamics simulations, to site-specifically interrogate the structure and hydration dynamics of the Trp41 gate in the transmembrane domain of the M2 proton channel. Our results suggest that the Trp41 sidechain adopts the t90 rotamer, the χ2 dihedral angle of which undergoes an increase of approximately 35° upon changing the pH from 7.4 to 5.0. Furthermore, we find that Trp41 is situated in an environment lacking bulk-like water, and somewhat surprisingly, the water density and dynamics do not show a measurable difference between the high (7.4) and low (5.0) pH states. Since previous studies have shown that upon channel opening water flows into the cavity above the histidine tetrad (His37), the present finding thus provides evidence indicating that the lack of sufficient water molecules near Trp41 needed to establish a continuous hydrogen bonding network poses an additional energetic bottleneck for proton conduction.
Related Literature
[Zn(H2O)4][Zn2Sn3Se9(MeNH2)]: a robust open framework chalcogenide with a large nonlinear optical response
Manolis J. Manos, Joon I. Jang, John B. Ketterson, Mercouri G. Kanatzidis
DOI: 10.1039/B712732D
Direct evidence for an iron(iv)-oxo porphyrin π-cation radical as an active oxidant in catalytic oxygenation reactions
Ah-Rim Han, Yu Jin Jeong, Yaeun Kang, Jung Yoon Lee, Mi Sook Seo, Wonwoo Nam
DOI: 10.1039/B716558G
Active peroxo titanium complexes: syntheses, characterization and their potential in the photooxidation of 2-propanol
Markus Rohe, Klaus Merz
DOI: 10.1039/B716199A
m-Benziporphodimethene: a new porphyrin analogue fluorescence zinc(ii) sensor
Chen-Hsiung Hung, Gao-Fong Chang, Anil Kumar, Geng-Fong Lin, Wei-Min Ching, Eric Wei-Guang Diau
DOI: 10.1039/B714412A
Towards technomimetic spoked wheels: dynamic hexakis-heteroleptic coordination at a hexakis-terpyridine scaffold
Michael Schmittel, Prasenjit Mal
DOI: 10.1039/B718185J
Univalent transition metal complexes of arenes stabilized by a bulky terphenylligand: differences in the stability of Cr(i), Mn(i) or Fe(i) complexes
Chengbao Ni, Bobby D. Ellis, James C. Fettinger, Gary J. Long, Philip P. Power
DOI: 10.1039/B715027J
Intramolecularcation–π interactions control the conformation of nonrestricted (phenylalkyl)pyridines
Isabella Richter, Jusaku Minari, Philip Axe, John P. Lowe, Tony D. James, Kazuo Sakurai, Steven D. Bull, John S. Fossey
DOI: 10.1039/B716937J
Synthesis of a coumarin compound from phenanthrene by a TiO2-photocatalyzed reaction
Suguru Higashida, Aiko Harada, Rikako Kawakatsu, Noriko Fujiwara, Michio Matsumura
DOI: 10.1039/B604332A
Tin-free radical alkylation of ketonesviaN-silyloxy enamines
Hyun-Ji Song, Che Jo Lim, Sunggi Lee, Sunggak Kim
DOI: 10.1039/B606295D
Facile preparation of water-soluble fluorescent silver nanoclusters using a polyelectrolyte template
Li Shang, Shaojun Dong
DOI: 10.1039/B717728C
You might also like
Are there alternatives to 1-(4-Chlorophenyl)-N-hydroxymethanimine (CAS: 3848-36-0) in synthesis?
When considering alternatives to 1-(4-Chlorophenyl)-N-hydroxymethanimine (CAS: 3...
How should (1R,9S,10S,12S,14E,16S,19R,20R,21S,22R)-3,9,21-Trihydroxy-5,10,12,14,16,20,22-heptamethyl-23,24-dioxatetracyclo[17.3.1.1~6,9~.0~2,7~]tetracosa-2,5,7,14-tetraen-4-one (CAS: 183202-73-5) be stored?
This compound should be stored in a cool, dry place away from direct sunlight. I...
How is 3-(4-Bromophenyl)-5-(2-fluorophenyl)-1,2,4-oxadiazole (CAS: 419553-16-5) typically synthesized?
3-(4-Bromophenyl)-5-(2-fluorophenyl)-1,2,4-oxadiazole is synthesized through a m...
How is 5-Chloro-2-(4-chlorophenyl)-4-methyl-6-[3-(1-piperidinyl)propoxy]pyrimidine (CAS: 1639220-19-1) typically synthesized?
5-Chloro-2-(4-chlorophenyl)-4-methyl-6-[3-(1-piperidinyl)propoxy]pyrimidine (CAS...
What industries use 2-Chloro-4-(difluoromethoxy)pyridine (CAS: 1206978-15-5)?
2-Chloro-4-(difluoromethoxy)pyridine is used in the pharmaceutical industry for ...
What regulatory guidelines apply to 3-Chloro-6-methylpyridazine (CAS: 1121-79-5)?
3-Chloro-6-methylpyridazine (CAS: 1121-79-5) is classified under the Globally Ha...
Are there alternatives to Methyl 4,5-dimethyl-2-nitrobenzoate in synthesis?
Several alternatives can be used in the synthesis of Methyl 4,5-dimethyl-2-nitro...
Are there alternatives to (2E,2'E)-3,3'-(1,4-Phenylene)bisacrylaldehyde in synthesis?
Alternatives to (2E,2'E)-3,3'-(1,4-Phenylene)bisacrylaldehyde include other acry...
What is 3-Amino-5-chloropyridin-2-ol hydrochloride (CAS: 1261906-29-9)?
3-Amino-5-chloropyridin-2-ol hydrochloride is an organic compound with the CAS n...
What precautions should be taken when handling 6,7-Difluoro-2,3-dihydro-4H-chromen-4-one (CAS: 1092349-93-3)?
When handling 6,7-Difluoro-2,3-dihydro-4H-chromen-4-one, it is essential to wear...
Source Journal
Physical Chemistry Chemical Physics

Physical Chemistry Chemical Physics (PCCP) is an international journal co-owned by 19 physical chemistry and physics societies from around the world. This journal publishes original, cutting-edge research in physical chemistry, chemical physics and biophysical chemistry. To be suitable for publication in PCCP, articles must include significant innovation and/or insight into physical chemistry; this is the most important criterion that reviewers and Editors will judge against when evaluating submissions. The journal has a broad scope and welcomes contributions spanning experiment, theory, computation and data science. Topical coverage includes spectroscopy, dynamics, kinetics, statistical mechanics, thermodynamics, electrochemistry, catalysis, surface science, quantum mechanics, quantum computing and machine learning. Interdisciplinary research areas such as polymers and soft matter, materials, nanoscience, energy, surfaces/interfaces, and biophysical chemistry are welcomed if they demonstrate significant innovation and/or insight into physical chemistry. Joined experimental/theoretical studies are particularly appreciated when complementary and based on up-to-date approaches.














