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

Slides:



Advertisements
Similar presentations
Ari Borthakur, PhD Associate Director, Center for Magnetic Resonance & Optical Imaging Department of Radiology Perelman school of Medicine, University.
Advertisements

General Info about Proteins Most diverse and most important macromolecules. Our entire DNA codes for proteins only, and nothing else. Therefore they are.
Magnetic Resonance Imaging Maurice Goldman Member Académie des sciences.
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Concept 5.4: Proteins have many structures, resulting in a wide range of functions.
S ASC Answer to Practice Problem
Petsko G.A., Ringe, D., Protein Structure and Function 2004, figure 5-5, pg Different ways to depict a protein structure Wire diagram Ribbon diagram.
Kcal/mol 5.7 X X X X X EIMSNMR.
Psy 8960, Fall ‘06 Introduction to MRI1 Introduction to MRI: NMR MRI - big picture –Neuroimaging alternatives –Goal: understanding neurall coding Electromagnetic.
Introduction to Molecular Biology zMolecular biology is interdisciplinary (biochemistry, genetics, cell biology) zImpact of genome projects (human, bacteria,
FMRI: Biological Basis and Experiment Design Intro History Basic mechanism Neurohemodynamic coupling.
Mossbauer Spectroscopy in Biological Systems: Proceedings of a meeting held at Allerton House, Monticello, Illinois. Editors: J. T. P. DeBrunner and E.
NUCLEAR MAGNETIC RESONANCE SPECTROSCOPY - an ideal tool for Diagnosis & Drug Design B. HASEENA BANU Asst.Professor,SriPadmavathi School of Pharmacy,Tiruchanoor,Tirupati.
Protein Basics Protein function Protein structure –Primary Amino acids Linkage Protein conformation framework –Dihedral angles –Ramachandran plots Sequence.
(Foundation Block) Dr. Ahmed Mujamammi Dr. Sumbul Fatma
Introduction to Molecular Biology zMolecular biology is interdisciplinary (biochemistry, genetics, cell biology) zImpact of genome projects (human, bacteria,
Watson and Crick(1953)- Double helix model of DNA
Proteins account for more than 50% of the dry mass of most cells
Medical Physics Physics 421 Course Description: Medical Physics is a course with two main parts:  Physics of the body  Physics of Diagnostic and Therapeutic.
Nuclear Magnetic Resonance (NMR) Spectroscopy Kurt Wuthrich Chemistry-2002 Richard Ernst Chemistry Felix Bloch & Edward Purcell Physics-1952 Paul.
Magnetic Resonance Contributions to Other Sciences Norman F. Ramsey Harvard University Principles of Magnetic Resonance First experiments Extensions to.
Proteins: Amino Acid Chains DNA Polymerase from E. coli Standard amino acid backbone: Carboxylic acid group, amino group, the alpha hydrogen and an R group.
Protein structure. BIOMEDICAL IMPORTANCE Protein function – Catalyze metabolic reactions – Power cellular motion – Provide structural integrity Defect.
PROTEINS PROTEINS Levels of Protein Structure.
NMR in Medicine and Biology
Amino acids and proteins … for AS Biology. Amino acids Proteins are macromolecules consisting of long unbranched chains of amino acids. All amino acids.
THE STRUCTURE AND FUNCTION OF MACROMOLECULES Proteins - Many Structures, Many Functions 1.A polypeptide is a polymer of amino acids connected to a specific.
13. Structure Determination: Nuclear Magnetic Resonance Spectroscopy
STRUCTURAL BIOLOGY Martina Mijušković ETH Zürich, Switzerland.
Magnetic Resonance Imaging – Basic Principles –
JG/10-09 NMR for structural biology DNA purification Protein domain from a database Protein structure possible since 1980s, due to 2-dimensional (and 3D.
Biomolecular Nuclear Magnetic Resonance Spectroscopy BASIC CONCEPTS OF NMR How does NMR work? Pulse FT NMR 2D NMR experiments nD NMR experiments 01/15/03.
Principles and Applications of NMR Spectroscopy Instructor: Tai-huang Huang (02)
1 FT NMR WORKSHOP/===/ S.A.I.F./===/ NEHU/==/ Shillong INTRODUCTORY LECTURE S.ARAVAMUDHAN CLICK HERE CLICK HERE for more.
Protein Structure and Bioinformatics. Chapter 2 What is protein structure? What are proteins made of? What forces determines protein structure? What is.
Major article in The Guardian 1999 Lucy Ellmann curls up with the latest tome Turns out it’s not enough to have invented the car, the bomb, fluorescent.
Magnetic Resonance Imaging Glenn Pierce, King’s College London, Department of Physics Introduction Edward Purcell and Felix Bloch were both awarded the.
First Principle Calculation of Nuclear Magnetic Resonance (NMR) chemical shift Kanchan Sonkar Center of Biomedical Magnetic Resonance SGPGIMS-Campus, Lucknow,
PROTEIN STRUCTURE (Donaldson, March 10,2003) What are we trying to learn about genes and their proteins: Predict function for unknown protein by comparison.
Levels of Protein Structure. Why is the structure of proteins (and the other organic nutrients) important to learn?
Levels of Protein Structure. Why is the structure of proteins (and the other organic nutrients) important to learn?
CHAPTER 5 THE STRUCTURE AND FUNCTION OF MACROMOLECULES Copyright © 2002 Pearson Education, Inc., publishing as Benjamin Cummings Section D: Proteins -
Biomolecular Nuclear Magnetic Resonance Spectroscopy
1 Modern Approaches to Protein structure Determination (6 lectures) Dr Matthew Crump.
Proteins Structures and Functions. What? A series of amino acids in a polypeptide chain Produced from the coding in the DNA of the nucleus Makes up.
CHM 708: MEDICINAL CHEMISTRY
HINDU COLLEGE OF PG COURSES
© SSER Ltd..
Lecture 5 Protein Structure
Topics for today: 1) A few comments on using NMR to investigate internal motions in biomolecules. 2) “MRI”, or Magnetic Resonance Imaging (The last day.
Nuclear magnetic resonance NMR spectroscopy is a key analytical technique for structure elucidation of a wide range of materials from small molecules to.
Macromolecules: Proteins
Fundamentals in Spectroscopy (in Biology)
Amino acids are linked by peptide bonds
1. Storage: plant/animal starch
Volume 9, Issue 2, Pages (February 2002)
Volume 85, Issue 7, Pages (June 1996)
NMR spectroscopy in post-genomic era AC 7121 Spring 2004
Hydration and DNA Recognition by Homeodomains
Volume 19, Issue 12, Pages (December 2011)
Volume 13, Issue 9, Pages (December 2015)
Crystal Structure of the MazE/MazF Complex
Structural Analysis of Ligand Stimulation of the Histidine Kinase NarX
Volume 91, Issue 5, Pages (November 1997)
Crystal Structure of the p53 Core Domain Bound to a Full Consensus Site as a Self- Assembled Tetramer  Yongheng Chen, Raja Dey, Lin Chen  Structure  Volume.
Functional Neuroimaging: a window on the working human brain
Volume 14, Issue 6, Pages (June 2006)
Structure of BamHI Bound to Nonspecific DNA
Crystal Structure of Skp, a Prefoldin-like Chaperone that Protects Soluble and Membrane Proteins from Aggregation  Troy A Walton, Marcelo C Sousa  Molecular.
PROTEINS.
Structures of osmosensory transporters.
Presentation transcript:

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