7.91 April 1, 2004 Amy Keating Protein structure Outline of the next part of the course Protein Structure Comparison classification 4/6 Principles of Molecular mechanics 48 X-ray crystallography and NMr 4/13 Modeling Mutants and Homologs 4/15 Threading and ab initio structure prediction 4/22 Computational Protein Design
Protein Structure Outline of the next part of the course 4/1 Protein Structure Comparison & Classification 4/6 Principles of Molecular Mechanics 4/8 X-ray crystallography and NMR 4/13 Modeling Mutants and Homologs 4/15 Threading and Ab Initio Structure Prediction 4/22 Computational Protein Design 7.91 April 1, 2004 Amy Keating
7.91 April 1, 2004 Amy Keating Introduction to protein Structure Classification Protein structures basics Where to find them how to look at them what they can tell you structural and evolutionary Comparisons PDB ID: 1HCL SchuIze-Gahmen, U, J Brandsen, H. D. Jones, D. O Morgan, L Meijer, J. Vesely, S.H. Kim. "Multiple Modes of Ligand Recognition: Crystal Structures of Cyclin-dependent Protein Kinase 2 in Complex with ATP and Two Inhibitors, Olomoucine and Isopentenyladenine. "Proteins 22 (1995): 378 TheProteinDataBank(pdb-http://www.pdb.org/)isthesingleworldwiderepositoryfortheprocessinganddistributionof3-dbiologicalmacromolecularstructuredata Berman, H. M.,J. Westbrook, Z Feng, G Gilland, T N. Bhat, H Weissig, I N. Shindyalov, and P. E Bourne. The Protein Data Bank. Nucleic Acids Research 28 (2000):235-242 (pDbAdvisoryNoticeonusingmaterialsavailableinthearchivehttp://www.rcsb.org/pdb/advisory.html
7.91 April 1, 2004 Amy Keating Introduction to Protein Structure & Classification Protein structures basics where to find them how to look at them what they can tell you structural and evolutionary comparisons PDB ID: 1HCL Schulze-Gahmen, U., J. Brandsen, H. D. Jones, D. O. Morgan, L. Meijer, J. Vesely, S. H. Kim. "Multiple Modes of Ligand Recognition: Crystal Structures of Cyclin-dependent Protein Kinase 2 in Complex with ATP and Two Inhibitors, Olomoucine and Isopentenyladenine." Proteins 22 (1995): 378. The Protein Data Bank (PDB - http://www.pdb.org/) is the single worldwide repository for the processing and distribution of 3-D biological macromolecular structure data. Berman, H. M., J. Westbrook, Z. Feng, G. Gilliland, T. N. Bhat, H. Weissig, I. N. Shindyalov, and P. E. Bourne. The Protein Data Bank. Nucleic Acids Research 28 (2000): 235-242 . (PDB Advisory Notice on using materials available in the archive: http://www.rcsb.org/pdb/advisory.html)
Review of protein structure hierarchy e Primary structure Glycine(Gly, G) Alanine (Ala, A) Valine(VaL v Leucine(Leu, L) Isoleucine (e, I) MAAAAAAGPEMVRGQVE 20 amino acids Phenylalanine (Phe, F Proline (Pro, Pl Methionine (Met, M) Tryptophan (Trp, w) hydrophobic/hydrophilic Polar, Hydrophillic R-groups acidic/basic large/small specialized(Gly, Pro, Cys) Serine(Ser, S) Threonine(Thr, T) Cysteine(Cys, C) Tyrosine (, Y) Asparagine (Asn, N) amine( GIn, O Electrically char ENIL. Lysine( Lys, K) Aspartic acid (Asp, D) Arginine (Arg, R
Review of protein structure hierarchy • Primary structure MAAAAAAGPEMVRGQVF • 20 amino acids – hydrophobic/hydrophilic – acidic/basic – large/small – specialized (Gly,Pro,Cys) C C O- O H Glycine (Gly, G) Alanine (Ala, A) Valine (Val, V) H H3 N+ C C O- O H CH3 CH3 CH3 H3 N+ C C O- O H CH H3N+ C C O- O H CH H3N+ H3C OH CH3 CH3 CH3 C C O- O H CH2 CH2 CH3 C C O- O H H3N+ CH2 CH2 C C O- O H H3 N+ CH2 S CH3 H3N+ C C O- O H H3 N+ CH2 C C O- O O H H3 N+ CH2 C C O- O H H3 N+ CH2 CH2 C NH2 C C C O- O H H3 N+ CH2 C C O- O H H2 N+ H2C C C O- O O H H3N+ CH2 C C O- O H H3 N+ CH2 CH2 - O C O C C O- O H H3 N+ CH2 CH2 CH2 CH2 NH3 + NH2 + NH+ NH C C O- O H H3N+ CH2 C C O- O H H3 N+ CH2 CH2 CH2 C NH NH2 - O C NH2 O CH2 CH NH 2 C C O- O H H3 N+ CH2 C C O- O H H3N+ CH2 SH OH C C O- O H H3 N+ CH OH Leucine (Leu, L) Isoleucine (IIe, I) Methionine (Met, M) Serine (Ser, S) Aspartic acid (Asp, D) Glutamic acid (Glu, E) Lysine (Lys, K) Arginine (Arg, R) Histidine (His, H) Threonine (Thr, T) Cysteine (Cys, C) Tyrosine (Tyr, Y) Asparagine (Asn, N) Glutamine (Gln, Q) Acidic Basic Phenylalanine (Phe, F) Tryptophan (Trp, W) Proline (Pro, P) Electrically charged Polar, Hydrophillic R-groups Nonpolar, Hydrophobic R-groups
N
O N N
N
O N N
N
O N N N O
N
O N N S
Representations of Protein Structure
Representations of Protein Structure
Review of protein structure hierarchy Secondary structure-why o you get regular secondary structure? a-helices β- - strands SGAYGSVCAA FDTKTGHRVA VKKLSRPFQS IIHAKRTYRE LRLLKHMKHE EEEE区E EEE EEEE HHHHHHHHH HHHHHH
Review of protein structure hierarchy • Secondary structure - why do you get regular secondary structure? α-helices β-strands SGAYGSVCAA FDTKTGHRVA VKKLSRPFQS IIHAKRTYRE LRLLKHMKHE EEEEEE EE EEE EEEE HHHHHHHHHH HHHHHH
Review of protein structure hierarchy Tertiary structure · Quaternary structure N-terminal domain of kinase hemoglobin Why do you get compact/globular tertiary structures?
Review of protein structure hierarchy • Tertiary structure • Quaternary structure N-terminal domain of kinase hemoglobin Why do you get compact/globular tertiary structures?