Sensitivity enhanced 14N/14N correlations to probe inter-beta-sheet interactions using fast magic angle spinning solid-state NMR in biological solids. Issue 32 (1st August 2016)

• Record Type: Journal Article
• Authors: Pandey, Manoj Kumar; Amoureux, Jean-Paul; Asakura, Tetsuo; Nishiyama, Yusuke
• Is Part Of: Physical chemistry chemical physics. Volume 18:Issue 32(2016)
• Page Start: 22583
• Page End: 22589
• Publication Date: 2016-08-01
• Subjects: Chemistry, Physical and theoretical -- Periodicals; 541.3
• DOI: 10.1039/c6cp03848d
• Languages: English
• ISSNs: 1463-9076

Abstract

Abstract : Sensitivity enhanced proton-detected 14 N/ 14 N correlation method mediated through accelerated 1 H– 1 H spin diffusion at fast magic angle spinning (MAS) solid-state NMR is demonstrated to distinguish inter-beta-sheet interactions in naturally abundant parallel and anti-parallel alanine tripeptides. Abstract : 14 N/ 14 N correlations are vital for structural studies of solid samples, especially those in which 15 N isotopic enrichment is challenging, time-consuming and expensive. Although 14 N nuclei have high isotopic abundance (99.6%), there are inherent difficulties in observing 14 N/ 14 N correlations due to limited resolution and sensitivity related to: (i) low 14 N gyromagnetic ratio ( γ ), (ii) large 14 N quadrupolar couplings, (iii) integer 14 N spin quantum number ( I = 1), and (iv) very weak 14 N– 14 N dipolar couplings. Previously, we demonstrated a proton-detected 3D 14 N/ 14 N/ 1 H correlation experiment at fast magic angle spinning (MAS) onl -histidine·HCl·H2 O utilizing a through-bond (J) and residual dipolar-splitting (RDS) based heteronuclear multiple quantum correlation (J-HMQC) sequence mediated through 1 H/ 1 H radio-frequency driven recoupling (RFDR). As an extension of our previous work, in this study we show the utility of dipolar-based HMQC (D-HMQC) in combination with 1 H/ 1 H RFDR mixing to obtain sensitivity enhanced 14 N/ 14 N correlations in more complex biological solids such as a glycyl-l -alanine (Gly-l -Ala) dipeptide, and parallel (P) and antiparallel (AP) β-strand alanine tripeptides (P-(Ala)3 and AP-(Ala)3, respectively). These systems highlight the mandatory necessity of 3D 14 N/ 14 N/ 1 H measurements to get 14 N/ 14 N correlations when the amide proton resonances are overlapped. Moreover, the application of long selective 14 N pulses, instead of short hard ones, is shown to improve the sensitivity. Globally, we demonstrate that replacing J-scalar with dipolar interaction and hard- with selective- 14 N pulses allows gaining a factor of ca. 360 in experimental time. On the basis of intermolecular NH/NH distances and 14 N quadrupolar tensor orientations, 14 N/ 14 N correlations are effectively utilized to make a clear distinction between the parallel and antiparallel arrangements of the β-strands in (Ala)3 through the observation of inter-β-sheet correlations.