BME 281 Presentation 2 – Ron Greene
“The few wonders of the world only exist while there are those with the sight to see them.” – Charles de Lint (Celtic folk musician )
1978 - Kurth Würthrich used NMR to determine protein structures
1981 - Don Wiley determined the structure of the hemagglutinin protein from the surface of the influenza virus
1998 - Rod MacKinnon publishes first high-resolution structure of an ion channel
2007 - Brian Kobilka solves first structure of a human G protein coupled receptor
1609 - Galileo Galilei develops compound microscope
1951 - Erwin Müller invents field ion microscope; sees first atoms
1964 - Aaron Klug shows Xray diffraction could be used to develop crystallographic electron microscopy
1971 - Protein Data Bank established as a repository for 3D structural data of proteins and nucleic acids
4pi – laser scanning flourescence microscope ~ 100nm scale
Xray crystallography – destroys subject material, no dynamic information
Nuclear Magnetic Resonance microscopy –capable of 1-2 Å resolution. Capable of imaging dynamic processes in vivo.
4π – FGP stained live yeast
H1receptor – Xray and NMR
Crystallized proteins
Spin – fundamental physical property of protons, electrons and neutrons
Nuclear Magnetic Resonance – a phenomenon which occurs in certain atoms when exposed to magnetic field
Elements with enough net spin resonate with detectable magnitudes
Gyroscopic ratio Larmor frequency
When placed in a magnetic field of strength B, a particle with a net spin can absorb a photon, of frequency ω. Chemical shift affects the Larmor frequency at which a given atom resonates
Chemical shift
Chemical shift is a precise metric of the chemical environment of an atom
After hitting with pulse to elevate energy states, NMR is measured by induction as nuclei relax to lower state
NMR signal contains many components, each with its own Larmor frequency
This signal, called Free Induction Delay (FID) decays with time
Fourier analysis is used to transform the signal from time domain to frequency domain.
“Here’s the plan: We put the band back together, do some gigs, earn some bread, bang!” – Jake Blues
The Future:
The Protein Data Bank continues to expand, including more proteins in more of their naturally occurring conformations
NMR microscopy and clinical MRI merge to offer real time imaging of biological processes on an atomic scale
REFERENCES[1] URI BME 281 BME Seminar II <www.ele.uri.edu/courses/bme281>.[2] J Puerta-Fonolla, T Vasquez-Osorio, J ruiz-Cabello, J Murillo-Gonzalez, A Pena-Melian. "Margentic resonance microscopy versus light microscopy in embryology teaching." Clinical Anatomy (2004): 429-435.[3] Oleg Yu Federoff, Miguel Salazar, Haiyong Han, Violetta Chemeris, Sean Kerwin, Laurence Hurley. "NMR-Based Model of a Telomerase-Inhibiting Compound Bound to G-quadruplex DNA." Biochemistry (1998): 12367-12374.[4] Seui Ogawa, david Tank, Ravi Menon, Juitta Ellerman, Seong-Gi Kim, Hellmut Merkle, Kamil Ugurbil. "Intrinsic signal changes accompanying sensory stiimulation: Functional brain mapping with magnetic resonabce imaging." Proceedings of the National Academy of Science (1992): 5951-5955.[5] wiki. "Nuclear magnetic Resonance." 22 October 2011. Wikipedia. 5 November 2011 <http://en.wikipedia.org/wiki/Nuclear_magnetic_resonance#NMR_spectroscopy>.
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