Atlas of Macromolecules for Protein Explorer Suggestions to Eric Martz. All images copyright © 2002 by Eric Martz. Click on any image for more information.

Contents Lesson Plans Enzymes Soluble Proteins (Not Enzymes) Signal Cascade Proteins (Intracellular) Structural Proteins Calcium-Binding Proteins Lipid Bilayers Integral Membrane Proteins Myristoylated Proteins DNA, RNA Proteins Complexed to Nucleic Acids (Transcription Factors, Polymerases etc.) Virus Capsids Immune System & Defense Molecules (Antibody, etc.) Toxins Carbohydrates Magnificent Molecular Machines Unusual Tertiary/Quaternary Structures Animated Morphs of Conformational Changes Evolutionary Conservation Protein Crystals History: Earliest Crystallographic Structures Other Browsable Lists of Molecules

STRAIGHTFORWARD
• Lysozyme, human, complexed to inhibitor, 1LZR (1965-1994). Hen egg white lysozyme was the first enzyme structure solved crystallographically (see history). Catalytic mechanism, 2001.
• Trypsin (porcine pancreatic) complexed to soybean trypsin inhibitor, 1AVX (1998).
• Carboxypeptidase A complexed with inhibitor, 1CBX (1992).
• Acetylcholinesterase complexed with huperzine inhibitor, 1VOT (1993-1997). SELECT Protein, DISPLAY Surface, then rotate until you can see the deep catalytic gorge containing the inhibitor.
• Lipase, 1LPM (1994). See animation of catalytic pocket opening.
• HIV protease with inhibitor, 4PHV (1991).
• Angiotensin-converting enzyme complexed with inhibitory drug lisinopril (licensed for treating hypertension), 1O86 (2003). Such inhibitors were developed without knowing the target protein structure, and on the assumption of mechanistic homology with carboxypeptidase A. This structure showed little if any such homology, but rather structural (but not sequence) homology to a family of zinc metalloproteases.
   
  CHALLENGING
• Animated simulation of the process of HIV protease inhibitor Ritonavir binding to the protease. This simulation is fictional, but chemically possible. The simulation was generated, starting with 1HXW (1997), by pulling the inhibitor out of the "side" of the protease with concurrent real-time energy minimization by molecular mechanics using Sculpt. Here are four animations saved from Protein Explorer's NMR/Animations page, emphasizing backbone, spacefill, contacts, or water. You can also view the animation in PE, where you can control the rendering and color scheme. Here are the scripts that produced the renderings and colorings in the previous four saved animations. Here is an alternative simulation in which the inhibitor was pulled out the "top" of the protease, opening the "lid". Here is more about animations.
• Succinyl Co-A synthetase, 1scu_1.mmol (1994). (The mmol tetramer was constructed by Probable Quaternary Structures as being a more probable specific oligomer than the tetramer in the asymmetric unit of 1SCU.)
• Calcineurin, a serine/threonine phosphatase with two metals in its catalytic site, a myristoylated regulatory chain with four bound calcium ions, complexed with the immunosuppresant drug FK506 and FK506-binding protein, 1TCO (1995). What is the state of the catalytic site?
• Glutamine synthetase, a twelve-chain homo-dodecamer, 1FPY (1995). See the overview of this molecule at Molecule of the Month.

STRAIGHTFORWARD
• Inositol 1,4,5-triphosphate bound to the ligand-binding domain of the endoplasmic-reticulum-membrane-associated calcium release channel, 1N4K (2002).

STRAIGHTFORWARD
• Myoglobin, oxy, 1MBO (1958-1980). The first protein structure solved crystallographically (see history).
• Myoglobin, deoxy, with all hydrogen atoms! 1CQ2 (2000). What was the experimental method? (See the PDB file header, EXPDTA record.)
• Hemoglobin, deoxy, 1HGA (1968-1992).
  See Oxygen-Binding Proteins tutorial at Biochemistry in 3D, and hemoglobin tutorial at UMass in English, auf Deutsch, in Portuguese.
• Insulin, 1APH (1982-1992).
• Green fluorescent protein, 1EMB (1997). 1EMB.
• Bone morphogenetic protein complexed with its inhibitor Noggin, described as "back-to-back butterflies" (Nature 420:613), 1m4u.mmol (2002). These secreted proteins control events in embryonic morphogenesis. Don't miss the cystine knots! (The complex is generated by Probable Quaternary Structures from the crystal asymmetric unit 1M4U.)

  See (under other categories)

• Calmodulin

  CHALLENGING

• Sickle cell hemoglobin (dimer of tetramers bound via mutant valine), 1HBS (1985). See hemoglobin tours at molvisindex.org. See procedure for aligning sickle Hb with wild type and viewing the mutant residue in the Guide to Using MSA3D.

Anthrax Toxins
• Review of the disease and the toxins, Mock & Fouet, Ann. Rev. Med. 55:647, 2001. See also Nature's Focus on Anthrax.
• Anthrax protective antigen, PA (1ACC, 1997) transports the lethal and edema factors through the cell membrane. The full length PA 735 AA chain, PA83, is cleaved to form the active fragment PA63, which forms heptamers. The publication linked to 1ACC describes the PA monomer and heptmer, but the 4.5A heptamer model was not deposited in the PDB. Robert Liddington kindly provided the heptamer model with permission to share it for educational purposes.
• Anthrax lethal factor alone, and complexed to its target MAPKK2, 1j7n_1.mmol vs. 1JKY (2001, 2001). (1j7n_1.mmol is extracted from the crystal dimer, 1J7N, by Probable Quaternary Structures.)
• Anthrax edema factor vs. edema factor complexed with calmodulin, 1K8T vs. 1k93_2.mmol (2002, 2002). Calmodulin activates the adenylyl cyclase exotoxin activity. (1k93_2.mmol is one dimer extracted from the original 1K93 hexamer by Probable Quaternary Structures.) See also other calmodulin structures.

STRAIGHTFORWARD
• Collagen fiber, 1CAG (1994).

• EF Hand binding calcium, animated, in Protein Morpher or Protein Explorer.
• Calmodulin:
  • With calcium, 1OSA (1994).
  • With calcium and bound portion of myosin light chain kinase, 2BBM (1992).
  • With calcium and bound portion of calcium-activated potassium channel, 1g4y.mmol (2001). First instance of calmodulin binding three alpha helices, with the N vs. C ends of calmodulin contacting different bound domains. (The complete tetramer is generated by Probable Quaternary Structures from the crystal asymmetric unit dimer 1G4Y.)
  • Previous two cases side by side, 2BBM vs. 1g4y.mmol.
  Morphed animations of calmodulin binding calcium and protein in Protein Morpher or Protein Explorer.

  See (under other categories)

• Anthrax edema toxin bound to calmodulin, with calmodulin in a new, extended conformation.
• Recoverin

  CHALLENGING

• Calmodulin, with calcium, NMR ensemble showing flexibility of interdomain linker, 1CFC (1995).
• Calmodulin, with calcium, complexed to fragment of myosin light chain kinase, NMR ensemble, 2BBN (1992).

STRAIGHTFORWARD
• 200-phospholipid hydrated bilayer theoretical models (2 megabytes each!) in crystalline, gel, and fluid conformations (Heller, Schaefer & Schulten, J. Phys. Chem. 97:8343, 1993; PDB files redistributed with permission).
  See snapshots and animated tutorial Lipid Bilayers and the Gramicidin Channel, Modelo de bicapa lipidica y canal de gramicidina.
  Figure at right (© 1996) "Five Bakers Dancing".
• More lipid bilayers and micelles.

STRAIGHTFORWARD
• Potassium channel, 1BL8 (1998, 3.2 Å). See another version below under "CHALLENGING".
• Aquaporin, a water channel, 1j4n.mmol (2001). (1j4n.mmol was assembled by Probable Quaternary Structures as a tetramer of the asymmetric unit in 1J4N.)
• A homo-heptameric membrane pore, Staphlococcal alpha-hemolysin, 7AHL (1996).
• Bacteriorhodopsin, a light-driven ion pump, 1C8R (1990 by electron diffraction, 1995 by X-ray, 1999). Has seven trans-membrane alpha helices with retinal and associated lipid. Note the buried water.
  See Bacteriorhodopsin tutorial at Biochemistry in 3D.
• Outer membrane iron transporter of E. coli, 1KMP (2002).
   
                       

  CHALLENGING

• Gramicidin channel in hydrated lipid bilayer, theoretical model (Crouzy, Woolf & Roux, Biophys. J. 67:1370, 1994; PDB file redistributed with permission).
  See snapshots and animated tutorial Lipid Bilayers and the Gramicidin Channel, Modelo de bicapa lipidica y canal de gramicidina.
• Potassium channel with four antibody Fab fragments bound (Caution, 1.2 megabytes) 1k4c.mmol (2001, 2.0 Å). (1k4c.mmol was assembled by Probable Quaternary Structures as a tetramer of the asymmetric unit in 1K4C.)
• Photosynthetic reaction center, purple bacterium, 1PRC (reported 1984, deposited in the Protein Data Bank 1988). This is the first high-resolution trans-membrane structure obtained by X-ray crystallography, earning its authors the 1988 Nobel Prize in Chemistry. (Here is a link to their original 1984 paper, not linked to the PDB record.)
• Photosynthetic reaction center with bacteriochlorophyll a, ubiquinone and iron, 1PSS (1994).
• Calcium pumping ATPase, with cytoplasmic and transmembrane domains, 1EUL (2000). Another conformation, based upon cryo-electron microscopy, provides a model for the catalytic cycle, 1KJU (2002).
   
  
• Porin, sucrose specific, Salmonella, water and sucrose in the pores, 1A0T (1998).
• Mechanosensitive channel, gated, "large", MscL homolog from Mycobacterium tuberculosis, 1MSL (1998).
• Mechanosensitive channel, voltage sensitive, E. coli MscS, 1MXM (2002).
• Outer membrane protein A of E. coli 1QJP (2000). Compare with NMR ensemble showing flexibility, 1G90 (2001).
• Chloride channel, 1kpl_1.mmol (2002). (1kpl_1.mmol is one dimer, extracted from the crystal tetramer 1KPL by Probable Quaternary Structures.)
• Succinate:quinone oxidoreductase (SQR), also the succinate dehydrogenase of the Krebs cycle, composed of four protein chains and five prosthetic groups, including a heme buried in the membrane, 1NEK (2003). This structure "reveals that electrons are tranferred in a path more than 40 Å in length from the succinate oxidation site at the FAD, by way of the three iron sulfur clusters, to the ubiquinone binding site".

Recoverin 1iku...1jsa

CHALLENGING
• Recoverin, a calcium-activated myristoyl switch, (Caution: NMR ensembles, >1 megabyte each) 1IKU (1995, without calcium, myristate buried) and 1JSA (1997, with calcium, myristate exposed).
  Brief introduction to recoverin and morphs of the transition, or morph animated in Protein Explorer.

  See also (under other categories)

• Calcineurin.

Genes were shown to reside in DNA in 1944 (Avery et al.) and this became widely accepted after the 1952 experiments of Hershey and Chase. The double helical structure of the DNA was predicted by James Watson and Francis Crick in 1953 (Nobel Prize, 1962). Their prediction was based in part upon X-ray diffraction studies by Rosalind Franklin, to whom Watson and Maurice Wilkins gave inadequate credit (see Rosalind Franklin: Dark Lady of DNA by Brenda Maddox, HarperCollins, 2002). The predicted B-form double helix was not confirmed with atomic-resolution crystal structures until 1973, first by using dinucleotides of RNA (Rosenberg et al.). The first crystal structure containing more than a full turn of the double helix was not solved until 1980 (Wing et al. 1BNA, 1981, 12 base pairs). The lag of more than a quarter century between prediction and empirical confirmation involved development of X-ray crystallography for macromolecules, and the need to produce a short, defined sequence of DNA for crystallization. This brief account is based upon a review by Berman, Gelbin, and Westbrook (Prog. Biophys. molec. Biol. 66:255, 1996), where the references will be found.

STRAIGHTFORWARD
• DNA double helix (B form), 12 base pairs, one turn, 1BNA (first full turn solved crystallographically, see above). This is an empirical crystallographic structure: notice the substantial and variable deviations from coplanarity for the base pairs. 112D (1986) has almost the same sequence, but can you find the mismatched base pair? (See Brown et al.).
  See tutorial Nucleotides at Biochemistry in 3D, and interactive DNA molecule at UMass in English, auf Deutsch, en Espagñol, in Portuguese.

  

• DNA double helix (B form), 36 base pairs (3 full turns), ideal theoretical model, DNA_B_FORM.PDB.
• DNA double helix (A form), 36 base pairs, ideal theoretical model, DNA_A_FORM.PDB.
• DNA double helix, 36 base pairs, B form side by side with A form.
• DNA double helix, 12 base pairs, Z-form.
• DNA double helix, 12 base pairs, B form side by side with Z form.
• Make your own sequence into A or B form DNA (or A form RNA), courtesy Pittsburgh Supercomputer Web Tools, Carnegie-Mellon University.
• Nucleotides, base pairs, and DNA forms at Glactone/Georgia State U.
• Atlas of Nucleic Acid-Containing Structures.

• DNA double helix, two turns of chromatin theoretical model, 171 base pairs, 1DNN.
• DNA/RNA hybrid double helix, 104D (1995).
• Transfer RNA (Phe), 4TNA (1974-1978). (1EHZ [2000] is a more challenging tRNA.)

  CHALLENGING

• Hammerhead ribozyme, 1hmh_1.mmol (1994). (1hmh_1.mmol is one dimer, extracted from the crystal hexamer 1HMH by Probable Quaternary Structures.)
  See Hammerhead Ribozyme tutorial at Biochemistry in 3D.

STRAIGHTFORWARD
• DNA polymerase complexed with DNA, 7ICG (1996).
• Lambda repressor complexed to DNA, 1LMB (1992).
  See Lac Repressor tutorial at Biochemistry in 3D.
• Zinc finger (Zif268) complexed to DNA, 1AAY (1996).
• TATA-box binding protein, human, complexed to DNA, 1CDW (1996).
• EcoRV endonuclease complexed to DNA, 1RVA (1995).
  See Endonuclease tutorial at Biochemistry in 3D.
• SarA transcriptional regulator of virulence factors in Staphylococcus aureus, 1FZP (2001).
  Morph "movie" of conformational change when SarA binds to DNA, see Animations in PE.
• HIN recombinase with specific contacts in both the major and minor grooves of the DNA double helix, 1HCR (1994).

  CHALLENGING

• RNA polymerase (T7 bacteriophage), with DNA template and nascent RNA, 1QLN (1999).
• Recombinase (Flp) with enclosed Holliday junction of DNA, 1FLO (2000).
• DNA mismatch repair protein MutS binding to a mismatch, 1E3M (2000). See if you can find the mismatch in the DNA double helix! To help, here is only the DNA and everything within 10 Å of the DNA (about 1,700 of the about 13,000 atoms in 1E3M). Another case of MutS with bound DNA is 1EWQ (2000): what is wrong with the DNA there? To help, here is only the DNA (and everything within 10 Å of the DNA). [These subsets of the atoms in the original PDB files were selected and saved with RasMol, following instructions available in PE's External Resources Window under Fewer or Single Chains. Access External Resources with the PE Site Map.]
• Ku heterodimer bound to DNA, 1JEY (2001). Facilitates double-strand DNA breaks by non-homologous end-joining. Encircles the DNA double helix with a steric fit, avoiding base contacts.

  ENORMOUS  

• Nucleosome with DNA, 1AOI (1997).  
• Ribosome, 70S, with 3 tRNA's and mRNA (phosphorus and alpha carbon atoms only). The 49 chains are provided in 2 PDB files (1GIX, 1GIY, 2001). A combined model with the sidechains missing is available at http://molvis.sdsc.edu/pdb/1gix1giy.pdb. Click here, or copy this URL and paste it into the long slot on the FrontDoor. This is a pseudo-NMR file, with the small subunit in model 1 and the large subunit in model 2. Find tours of the ribosome at molvisindex.org.
• Ribosome, small subunit (30S), 22 chains with sidechains (CAUTION, 1.1 megabytes*), 1FJF (2000).
• Ribosome, large subunit (50S), 29 chains with sidechains (CAUTION, 1.3 megabytes*), 1FFK (2000).

ENORMOUS

• SV40 whole virus capsid (CAUTION: 3 megabytes*, alpha carbons only), based on the homopentamer (+1) of the VP1 capsid protein in 1SVA (1996). The whole capsid (about 70 megabytes with all sidechains) is available from Probable Quaternary Structures. After removing all but the alpha carbons (with PDB Tools), the resulting 12 megabyte PDB file was gzipped to less than 3 megabytes in file 1sva-cao.mmol (alpha carbons only). The 360 chains in this mmol file greatly exceed the number that PE (or Chime) can handle gracefully, but all are displayed showing a complete capsid. The 360 chains are arranged in 72 pentamers, which in turn are arranged to form a 12-faced icosahedron.
• Simplified model of SV40 capsid, displayed using a custom Chime script. Each of the 360 chains has been reduced to a single atom, and the enclosing icosahedron is represented. (This script cannot yet be effectively displayed in PE -- it awaits completion of PIPE.)
   
  

• "Protein chainmail" virus capsid, bacteriophage HK97, (CAUTION: 2 megabytes*) entire capsid, alpha carbon atoms only, 1fh6_cao.mmol. This capsid matures by autocatalytic formation of 420 covalent isopeptide bonds between the side chains of lysine 169 and asparagine 356. (These isopeptide bonds are not easily visualized with the PDB files available here.) (1fh6_cao.mmol was assembled from 1FH6 by Probable Quaternary Structures.)
  
• sTALL-1, a cytokine proposed to function as a 60-chain homomultimer very similar to a virus capsid. The possible evolutionary relation to capsids of small RNA plant viruses is intriguing.

CHALLENGING

• Bacterial cell wall puncturing device of bacteriophage T4, aka tail lysozyme, (Caution: 1.6 megabytes) 1k28.mmol (2002). (This hexamer was generated from the dimer in the asymmetric unit of 1K28 by Probable Quaternary Structures.)
• Proteasome (28 chains, 1.2 megabytes*), 1PMA (1995). From the archeon Thermoplasma acidophilum.
• HslU protease/HslV chaperone complex (24 chains, 1.0 megabytes*), 1G3I (2000). From Hemophilus influenzae.
• Chaperonin, GroEL-GroES (21 chains, 1.3 megabytes*), 1AON (1997). From E. coli.

  SEE ALSO (under other categories)

• The Ribosome.
• The Nucleosome.

STRAIGHTFORWARD
    Antibody
• Complete IgG antibody, 1IGT (1997).
  See interactive antibody tutorial at UMass in English, auf Deutsch.
• Complete IgG antibody with finger-like loop able to fit into the crevice in HIV gp120 that accomodates CD4, 1HZH (2001). The finger-like loop is heavy chain CDR3, 18 residues numbered 94-101 (including inserted residues numbered 100A-100J). A synthetic peptide mimicking this CDR H3 neutralized HIV.
• Fab fragment of antibody bound to lysozyme antigen, 1FDL (1991).
      MHC
• Major histocompatibility complex, class I, with viral peptide, 2VAA (1992). To compare with a different viral peptide, display 2VAA side by side with 2VAB. See detailed instructions for Immunology Class.
  See MHC tutorials at Biochemistry in 3D and at
• Major histocompatibility complex, class II, with peptide from lysozyme, 1f3j_1.mmol (2000). (One copy of this complex was extracted from the crystal dimer in the asymmetric unit of 1F3J by Probable Quaternary Structures.)
      Cytokines
• Interferon Gamma, bovine, expressed in E. coli, 1D9C (2000).
• Interleukin-4 complexed to alpha-chain of receptor, human, expressed in E. coli, 1IAR (1999).
• Interleukin-1 receptor complexed to IL-1 receptor antagonist, human, expressed in E. coli, 1IRA (1997).
• Chemokine IL-8, human (mutated), expressed in E. coli, 1ICW (1997).  
• sTALL-1 cytokine of the TNF superfamily, human, soluble fragment expressed in E. coli, 1jh5_cao.mmol (2001; alpha carbons only).
  This 60-chain homo-multimer, proposed to be the functional form of this cytokine, is generated by Probable Quaternary Structures from the crystal asymmetric unit of 1JH5. This virus-capsid-like assembly is very similar to capsids of the smallest plant RNA viruses, raising the question of which came first.
  
  
      Immuno-Receptors
• CTLA-4 bound to B7-1 (external domains only), 1I8L (2001). The divalent homodimers of both molecules are believed to form chains in the immunological synapse.  
• Defensin (Rhesus theta defensin one, RTD-1), an antibacterial cyclic 18-amino acid peptide, 1HVZ (20-model NMR strcture, 2001). Each half is coded by a different gene. Cyclization is thought to increase resistance to exoproteases (Trabi & Craik, TiBS 27:132).
  

  CHALLENGING

• CD4 (human) complexed to HIV gp120 and Fab (human), 1G9M (2000).
• CD8 complexed to MHC class I, 1BQH (1998). Only the terminal domains of the CD8 alpha-alpha homodimer are present. The MHC class I in this complex is H-2Kb with VSV8 peptide (same as 2VAA above).
• T Cell Receptor (ab), complexed to HTLV1 viral peptide presented by HLA-A2, 1AO7 (1996).
• T Cell Receptor (gd), 1hxm_4.mmol (2001). (One copy of the heterodimer was extracted from four copies in the crystal asymmetric unit of 1HXM by Probable Quaternary Structures.)

• Capsular polysaccharide, E. coli, 1CAP (1977).
• Chondroitin-4-sulfate, sodium salt, 1C4S (1978).
• Heparin (2-model NMR structure) 1HPN (1993).

• A deeply knotted protein chain, 1QMG (2000). You won't be able to discern the knot by simple observation. See Knots in Proteins for an explanation and convincing visualizations.
• The cyclic cystine knot (CCK) motif involves penetration of a small ring, formed by two disulfide bonds and their connecting peptide backbone segments, by a third disulfide bond (Trabi & Craik, TiBS 27:132). Found in plant defense proteins called cyclotides, the first CCK structure reported was that of 1KAL (10-model NMR structure, 1995).
• Intrinsically disordered chains that fit together in a stable heterodimer via "mutual synergistic folding". The heterodimer between p160 receptor coactivator and CBP/p300 transcriptional coactivator, 1KBH (2002), is a member of a family of ligand-activated transcription factors involved in nuclear hormone receptors.
• Chaperone SicP maintaining Salmonella SptP virulence effector protein (105 residues) in a largely "unfolded" state, presumably to facilitate type III secretion, 1JYO (2001).
• Naturally-occurring cyclic peptides.
• sTALL-1, a cytokine proposed to function as a 60-chain homomultimer very similar to a virus capsid. The possible evolutionary relation to capsids of small RNA plant viruses is intriguing.

Suggestions to Eric Martz.
 
* PDB file sizes marked "*" are given for gzipped files, as they will be transferred from the Protein Data Bank (or other servers) to Chime when the above links are clicked. If you save the plain text PDB file to disk from Chime/PE, it will be about 4-fold larger.
 
Alpha-carbons only: Some very large structures are supplied as alpha-carbons only. This enables the backbone to be viewed, but not secondary structure (and therefore also not schematic "cartoon" rendering). To see secondary structure, you'll have to get the complete structure (usually available from EBI's Probable Quaternary Structures), but it is typically multiple megabytes in size.