Introduction NMR spectroscopy in post-genomic era AC 7121 Spring 2004

Nobel for Magnetic Resonance Isador I. Rabi Nobel Prize in Physics, 1944 For his resonance method for recording the magnetic properties of atomic nuclei. Felix Bloch and Edward M. Purcell, USA Nobel Prize in Physics, 1952 The NMR phenomenon was demonstrated for protons in 1946.

Richard Ernst, Zurich, Nobel Prize in Chemistry, 1991 For his fundamental contributions to NMR methodology-Nuclear Magnetic Resonance Fourier Transform Spectroscopy Kurt Wüthrich Nobel Prize in Chemistry, 2002 NMR studies of structure and function of biological macromolecules Nobel for Magnetic Resonance

Paul C. Lauterbur (Urbana, IL) and Sir Peter Mansfield (Nottingham, UK) Nobel Prize in Physiology or Medicine, 2003 For their pioneering contributions which led to the application of magnetic resonance in medical imaging.

Nobel for Magnetic Resonance Alexeij A. Abrikosow (Argonne, IL) and Vitalij L. Ginzburg (Moscow) Nobel Prize in Physics, 2003 For pioneering contributions to the theory of type-II superconductors, i.e., those alloys capable of withstanding the high magnetic fields that occur in MR applications.

ATSTVTGGYAQSDAQGQMNKMGGFNLKYRYEEDNSPLGVIGSFTYTEKSRTASSGDYNKNQYYGITAGP AYRINDWASIYGVVGVGYGKFQTTEYPTYKNDTSDYGFSYGAGLQFNPMENVALDFSYEQSRIRSVDVG TWIAGVGYRF tctagacttaagtaaagcgtggagtgtactggatatacccaatgctggttgagcatttgttgaaaaaattttcccccgttttgactaaaatgcgccaggattgatggaatcat tagtctggtgattaggaataatctggatgaatgacagggaaaacatgcgtaatacttacgcagttctctgaaaaagtgatttaaatttagatggatagcggtgtatggaaa cgttctgttacatgaaatggcccgttagacatcacaaatcgcgaagagtttcccattaatttttgatatatttaaaacttaggacttatttgaatcacatttgaggtggttatgaa aaaaattgcatgtctttcagcactggccgcagttctggctttcaccgcaggtacttccgtagctgcgacttctactgtaactggcggttacgcacagagcgacgctcagg gccaaatgaacaaaatgggcggtttcaacctgaaataccgctatgaagaagacaacagcccgctgggtgtgatcggttctttcacttacaccgagaaaagccgtactg caagctctggtgactacaacaaaaaccagtactacggcatcactgctggtccggcttaccgcattaacgactgggcaagcatctacggtgtagtgggtgtgggttatgg taaattccagaccactgaatacccgacctacaaacacgacaccagcgactacggtttctcctacggtgcgggtctgcagttcaacccgatggaaaacgttgctctgga cttctcttacgagcagagccgtattcgtagcgttgacgtaggcacctggattgccggtgttggttaccgcttctaatcactttggtgatataaaaaatccgcctctcggggc ggatttttgtttttaaggtttcgggtcgaaaatatc Outer Membrane Protein Ompx from Escherichia Coli From Sequence to function Example 1 Ompx from E.Coli

From Sequence to function Example 2GLUTAMINE SYNTHETASE from Salmonella typhimuriumSalmonella typhimurium MSAEHVLTMLNEHEVKFVDLRFTDTKGKEQHVTIPAHQVNAEFFEEGKMFDGSSIGGWKGINESDMVLMPDASTA VIDPFFADSTLIIRCDILEPGTLQGYDRDPRSIAKRAEDYLRATGIADTVLFGPEPEFFLFDDIRFGASISGSHVAIDDIE GAWNSSTKYEGGNKGHRPGVKGGYFPVPPVDSAQDIRSEMCLVMEQMGLVVEAHHHEVATAGQNEVATRFNTM TKKADEIQIYKYVVHNVAHRFGKTATFMPKPMFGDNGSGMHCHMSLAKNGTNLFSGDKYAGLSEQALYYIGGVIK HAKAINALANPTTNSYKRLVPGYEAPVMLAYSARNRSASIRIPVVASPKARRIEVRFPDPAANPYLCFAALLMAGLD GIKNKIHPGEPMDKNLYDLPPEEAKEIPQVAGSLEEALNALDLDREFLKAGGVFTDEAIDAYIALRREEDDRVRMTP HPVEFELYYSV GLUTAMINE SYNTHETASE

From Sequence to function Example 3Antennapedia homeodomain The polypeptide chain in this protein is partially folded, with both ends showing pronounced disorder. In complex with its operator DNA, the N-terminal chain end is located in the minor groove of the DNA, where the polypeptide adopts a well-defined structure.

Solution Structure Of The Alzheimer'S Disease Amyloid  - Peptide (1-42) From Sequence to function Example 4Amyloid peptide 1IYT Two Types of Alzheimer’s  -Amyloid (1–40) Peptide Membrane Interactions: Aggregation Preventing ransmembrane Anchoring Versus Accelerated Surface Fibril Formation 1RVS Structure Of Transthyretin In Amyloid Fibrils Determined By Solid-State Magic Angle Spinning NMR

From Sequence to function Example 4Amyloid peptide Solution Structure Model of Residues 1-28 of the Amyloid -Peptide When Bound to Micelles J. Am. Chem. Soc.; 1998; 120(43) pp

This view shows haemoglobin cycling between the oxygen bound and the oxygen free states. As it does so, the molecule opens up or closes, to allow O 2 (the two red spheres) to float away or bind to the haem moeity (shown in space filling model). N.B. Haemoglobin naturally aggregates as groups of four molecules, 2 alpha and 2 beta chains. They are shown in monochrome here, but the four-fold aggregation is the reason for four oxygen molecules appearing in the animation. From Sequence to function Example 5Hemoglobin 1HHO and 4HHB

This animated figure illustrates the motion of the     dimer (thick coils towards front) relative to the     dimer (thin coils towards rear) in the oxy-to- deoxy transition. Here, the coordinates of oxy- and deoxy-Hb have been superimposed at the     interface so that the     dimer remains stationary. The     dimer rotates by 15 degrees about an axis passing through the  subunits. From Sequence to function Example 5 Hemoglobin

Schematic drawing of the insertion of gp41- FP into the SDS micelle and its interaction with the 5- and 12-DXSA probes. A15 to G16 are depicted at the micelle-water interface, while 12- and 5-DXSA are near F8/L9 and 14, espectively. From Sequence to function Example 6Envelope Glycoprotein of HIV-1 gp41 fusion peptide in aqueous solution. L7~F11 adopt a Type-I  turn. gp41 fusion peptide in 50% TFE.

From Sequence to function Structural genomics Structural genomics Proteins whose primary sequences are encoded in the genomes mediate most of the chemical reactions occurring in a living organism. Their three-dimensional structures can provide hints to an understanding of their functions and, ultimately, to an understanding of the chemical bases of life itself. Therefore, research leading to a complete coverage of protein structures logically follows the determination of genome sequences. Structural genomics is the field of science focused on the systematic determination of the three-dimensional structure of the proteins encoded into genomes. Ivano Bertini in Acc. Chem. Res.v36, 3, p

Yee et. al. Acc. Chem. Res.v36, 3, p From Sequence to function

atgggaattg actacgtggt gttttacctc atacccaata tagtgggcgg cttttatatg 61 tttattatgg cgctgggggc ggccaagagg ccgagaagcc acgcctatcc cccgtggag aactacctcg tcgttgtagt tactgtgggc gatgagaggg taatgccggc tttagcggag accgtggccc agctggagag gctggggctg aggtacacag tgctctcctc ccgccccctc cccattaaaa accacatagt agtgccaaaa aagaggacg gctctaaata ccgcgcaatt ctctggttcg ttaagaatta cgccagaaac gacatgtggt atatcttcct tgacgacgac agctacccat tagatacccg atttttacgc gatattgcat attacggagc caggggatgc gtggctggca acggcgtgtt agtgccgagg cccggccgct cagccctcgc atacgcctta gactggatta ggtatttcca cgacttaact cataccgct tttccctcga ggtgctcaga aggcctatat tcggcatgca cggggaattg ttaatagtga ggggggatgt gttgaggagc atctggccgg ctatgggcga caccattacg gaggatttcc gcttcgccat ggagctctta aagcgcaggt acaagacttt tcaaacctcc acaagggtct caattaaaag ccccaactcc ctgagggact tcgtaagaca gagggccagg ggcggcgg tatatcaga ggccgccaag tataaaaacg cctattactt aatcctaacg gcctctccca tcgccctctt cctctcaacc ccggccagct ggctatacgg cttcacaata cccctcttaa tctccgcagt ctacgcctcg gtgtatatat acggtagctt aaaggcgaaa aggtatatat tagacgtgtg gctagcctca tttcttgaat taatgggctt aataatcggc ccgcgagaa aggcgaagaa cttctacgta atagacaaga ggtag From Sequence to function

From Structure to function

nature structural biology structural genomics supplement november 2000 p991 From Structure to function

nature structural biology structural genomics supplement november 2000 Potential impacts on drug discovery

Resources on the Web Protein Data Bank

Resources on the Web BioMagResBank