List of biophysically important macromolecular crystal structures

File:Myoglobin helix cylinder sketch.jpg

File:Helix electron density myoglobin 2nrl 17-32.jpg

1958{{snd}} Myoglobin was the very first crystal structure of a protein molecule.{{cite journal |vauthors=Kendrew JC, Bodo G, Dintzis HM, Parrish RG, Wyckoff H, Phillips DC |title=A Three-Dimensional Model of the Myoglobin Molecule Obtained by X-Ray Analysis |year=1958 |journal=Nature |volume=181 |pages=662–666 |doi=10.1038/181662a0 |issue=4610 |pmid=13517261 |bibcode=1958Natur.181..662K }} Myoglobin cradles an iron-containing heme group that reversibly binds oxygen for use in powering muscle fibers, and those first crystals were of myoglobin from the sperm whale, whose muscles need copious oxygen storage for deep dives. The myoglobin 3-dimensional structure is made up of 8 alpha-helices, and the crystal structure showed that their conformation was right-handed and very closely matched the geometry proposed by Linus Pauling, with 3.6 residues per turn and backbone hydrogen bonds from the peptide NH of one residue to the peptide CO of residue i+4. Myoglobin is a model system for many types of biophysical studies,{{cite journal |vauthors=Frauenfelder H, McMahon BH, Fenimore PW |title=Myoglobin: the hydrogen atom of biology and a paradigm of complexity |year=2003 |journal=Proceedings of the National Academy of Sciences USA |volume=100 |issue=15 |pages=8615–8617 |doi=10.1073/pnas.1633688100|pmid=12861080 |pmc=166357 |bibcode=2003PNAS..100.8615F |doi-access=free }} especially involving the binding process of small ligands such as oxygen and carbon monoxide.

File:Hemoglobin beta red whBkg.tif

File:Hemoglobin t-r state ani.gif

1960{{snd}} The hemoglobin crystal structure{{cite journal |vauthors=Perutz MF, Rossmann MG, Cullis AF, Muirhead H, North AC |title=Structure of haemoglobin: A three-dimensional Fourier synthesis at 5.5-Å resolution, obtained by X-ray analysis |year=1960 |journal=Nature |volume=185 |pages=416–422 |doi=10.1038/185416a0 |pmid=18990801 |issue=4711|bibcode=1960Natur.185..416P |s2cid=4208282 }} showed a tetramer of two related chain types and was solved at much lower resolution than the monomeric myoglobin, but it clearly had the same basic 8-helix architecture (now called the "globin fold"). Further hemoglobin crystal structures at higher resolution (PDB 1MHB, 1DHB) soon showed the coupled change of both local and quaternary conformation between the oxy and deoxy states of hemoglobin,{{cite journal |author=Perutz MF |title=Stereochemistry of Cooperative Effects in Haemoglobin: Haem–Haem Interaction and the Problem of Allostery |year=1970 |journal=Nature |volume=228 |pages=726–734 |doi=10.1038/228726a0 |pmid=5528785 |issue=5273|bibcode=1970Natur.228..726P |s2cid=43624891 }} which explains the cooperativity of oxygen binding in the blood and the allosteric effect of factors such as pH and DPG. For decades hemoglobin was the primary teaching example for the concept of allostery, as well as being an intensive focus of research and discussion on allostery. In 1909, hemoglobin crystals from >100 species were used to relate taxonomy to molecular properties.{{cite book |author1=Edward Tyson Reichert |author2=Amos Peaslee Brown |name-list-style=amp|title=The Differentiation and Specificity of Corresponding Proteins and other Vital Substances in Relation to Biological Classification and Organic Evolution: The Crystallography of Hemoglobins |url=https://archive.org/details/cu31924003153263 |year=1909 |publisher=Carnegie Institution |location=Washington, DC}} That book was cited by Perutz in the 1938 report{{cite journal |vauthors=Bernal JD, Fankuchen I, Perutz M |title=X-ray study of chymotrypsin and hemoglobin |year=1938 |journal=Nature |volume=141 |issue=3568 |pages=523–524|doi=10.1038/141523a0 |bibcode=1938Natur.141..523B |s2cid=4063748 }} of horse hemoglobin crystals that began his long saga to solve the crystal structure. Hemoglobin crystals are pleochroic {{emdash}} dark red in two directions and pale red in the third {{emdash}} because of the orientation of the hemes, and the bright Soret band of the heme porphyrin groups is used in spectroscopic analysis of hemoglobin ligand binding.

File:HEW lysozyme rib bw.tif

1965{{snd}} Hen-egg-white lysozyme (PDB file 1lyz).{{cite journal |vauthors=Blake CC, Koenig DF, Mair GA, North AC, Phillips DC, Sarma VR |title=Structure of hen egg-white lysozyme: A three-dimensional Fourier synthesis at 2Å resolution |year=1965 |journal=Nature |volume=206 |pages=757–761 |doi=10.1038/206757a0 |pmid=5891407 |issue=4986|bibcode=1965Natur.206..757B |s2cid=4161467 }} was the first crystal structure of an enzyme (it cleaves small carbohydrates into simple sugars), used for early studies of enzyme mechanism.{{cite journal |vauthors=Warshel A, Levitt M |title=Theoretical studies of enzymic reactions: Dielectric, electrostatic, and steric stabilization of the carbonium ion in the reaction of lysozyme |year=1976 |journal=J Mol Biol |volume=103 |issue=2 |pages=227–49|pmid=985660 |doi=10.1016/0022-2836(76)90311-9}} It contained beta sheet (antiparallel) as well as helices, and was also the first macromolecular structure to have its atomic coordinates refined (in real space).{{cite journal |author=Diamond R |title=Real-space refinement of the structure of hen egg-white lysozyme |year=1974 |journal=Journal of Molecular Biology |volume= 82 |issue=3 |pages=371–374 |doi=10.1016/0022-2836(74)90598-1|pmid=4856347 }} The starting material for preparation can be bought at the grocery store, and hen-egg lysozyme crystallizes very readily in many different space groups; it is the favorite test case for new crystallographic experiments and instruments. Recent examples are nanocrystals of lysozyme for free-electron laser data collection{{cite journal |vauthors=Boutet S, Lomb L, Williams GJ, etal |title=High-resolution protein structure determination by serial femtosecond crystallography |year=2012 |journal=Science |volume=337 |issue=6092 |pages=362–364|doi=10.1126/science.1217737 |pmid=22653729 |pmc=3788707 |bibcode=2012Sci...337..362B |url=http://bib-pubdb1.desy.de/record/140575/files/lysozyme-all.pdf }} and microcrystals for micro electron diffraction.{{cite journal |vauthors=Shi D, Nannenga BL, Iadenza MG, Gonen T |title=Three-dimensional electron crystallography of protein microcrystals |year=2013 |journal=eLife |volume=2 |pages=e01345 |doi=10.7554/elife.01345|pmid=24252878 |pmc=3831942 |doi-access=free }}

File:RibonucleaseA SS paleRib.png

1967{{snd}} Ribonuclease A (PDB file 2RSA){{cite journal |vauthors=Kartha G, Bello J, Harker D |title=Tertiary structure of ribonuclease |year=1967 |journal=Nature |volume=213 |pages=862–865 |doi=10.1038/213862a0 |pmid=6043657 |issue=5079|bibcode=1967Natur.213..862K |s2cid=4183721 }} is an RNA-cleaving enzyme stabilized by 4 disulfide bonds. It was used in Anfinsen's seminal research on protein folding which led to the concept that a protein's 3-dimensional structure was determined by its amino-acid sequence. Ribonuclease S, the cleaved, two-component form studied by Fred Richards, was also enzymatically active, had a nearly identical crystal structure (PDB file 1RNS),{{cite journal |vauthors=Wyckoff HW, Hardman KD, Allewell NM, Inagami T, Johnson LN, Richards FM |title=The structure of ribonuclease-S at 3.5 Å resolution |year=1967 |journal=Journal of Biological Chemistry |volume=242 |issue=17 |pages=3984–3988|doi=10.1016/S0021-9258(18)95844-8 |doi-access=free |pmid=6037556 }} and was shown to be catalytically active even in the crystal,{{cite journal |vauthors=Doscher MS, Richards FM | year=1963| title=The activity of an enzyme in the crystalline state: Ribonuclease-S| journal=Journal of Biological Chemistry| volume=238| issue=7| pages=2399–2406| doi=10.1016/S0021-9258(19)67984-6| doi-access=free}} helping dispel doubts about the relevance of protein crystal structures to biological function.

File:Elastase ribbon BW.jpg

1967{{snd}} The serine proteases are a historically very important group of enzyme structures, because collectively they illuminated catalytic mechanism (in their case, by the Ser-His-Asp "catalytic triad"), the basis of differing substrate specificities, and the activation mechanism by which a controlled enzymatic cleavage buries the new chain end to properly rearrange the active site.{{cite book |vauthors=Dickerson RE, Geis I |title=Structure and Action of Proteins |url=https://archive.org/details/structureaction00dick |year=1969 |publisher= Harper |location=New York}} The early crystal structures included chymotrypsin (PDB file 2CHA),{{cite journal |vauthors=Matthews BW, Sigler PB, Henderson R, Blow DM |title=Three-dimensional structure of tosyl-α-chymotrypsin |year=1967 |journal=Nature |volume=214 |pages=652–656 |doi=10.1038/214652a0 |pmid=6049071 |issue=5089|bibcode=1967Natur.214..652M |s2cid=4273406 }} chymotrypsinogen (PDB file 1CHG),{{cite journal |vauthors=Freer ST, Kraut J, Robertus JD, Tonle H, Wright HT |title=Chymotrypsinogen: 2.5-Å crystal structure, comparison with α-chymotrypsin, and implications for zymogen activation |year=1970 |journal= Biochemistry |volume=9 |pages=1997–2009 |doi=10.1021/bi00811a022 |pmid=5442169 |issue=9}} trypsin (PDB file 1PTN),{{cite journal |vauthors=Fehlhammer H, Bode W |title=The refined crystal structure of bovine beta-trypsin at 1.8Å resolution, II. Crystallographic refinement, calcium binding site and active site at pH 7.0 |year=1975 |journal=Journal of Molecular Biology |volume=98 |issue=4 |pages=693–697|doi=10.1016/s0022-2836(75)80005-2 |pmid=512 }} and elastase (PDB file 1EST).{{cite journal |vauthors=Sawyer L, Shotton DM, Campbell JW, Ladner RC |title=The atomic structure of crystalline porcine pancreatic elastase at 2.5Å resolution: comparison with the structure of alpha-chymotrypsin |year=1978 |journal=Journal of Molecular Biology |volume=118 |issue=2 |pages=137–208 |doi=10.1016/0022-2836(78)90412-6|pmid=628010 }} They also were the first protein structures that showed two near-identical domains, presumably related by gene duplication. One reason for their wide use as textbook and classroom examples was the insertion-code numbering system, which made Ser195 and His57 consistent and memorable despite the protein-specific sequence differences.{{cn|date=January 2024}}

1968{{snd}} Papain

File:Carboxypeptidase-A rib bw.tif

File:Potato CPA inhibitor ribbon.jpg

1969{{snd}} Carboxypeptidase A is a zinc metalloprotease. Its crystal structure (PDB file 1CPA){{cite journal |author1=Lipscomb WN |author2=Hartsuck JA |author3=Reeke GN |author4=Quiocho FA |author5=Bethge PH |author6=Ludwif=g ML |author7=Steitz TA |author8=Muirhead H |author9=Coppola JC |title= The structure of carboxypeptidase A, VII. The 2.0-Å resolution studies of the enzyme and of its complex with glycyltyrosine, and mechanistic deductions |year=1969 |journal=Brookhaven Symposia in Biology |volume= 21 |issue=1 |pages=24–90|pmid=5719196 }} showed the first parallel beta structure: a large, twisted, central sheet of 8 strands with the active-site Zn located at the C-terminal end of the middle strands and the sheet flanked on both sides with alpha helices. It is an exopeptidase that cleaves peptides or proteins from the carboxy-terminal end rather than internal to the sequence. Later a small protein inhibitor of carboxypeptidase was solved (PDB file 4CPA){{cite journal |vauthors=Rees DC, Lipscomb WN |title=Refined crystal structure of the potato inhibitor complex of carboxypeptidase A at 2.5 A resolution |year=1982 |journal=Journal of Molecular Biology |volume=160 |issue=3 |pages=475–498 |doi=10.1016/0022-2836(82)90309-6|pmid=7154070 }} that mechanically stops the catalysis by presenting its C-terminal end just sticking out from between a ring of disulfide bonds with tight structure behind it, preventing the enzyme from sucking in the chain past the first residue.

Image:Subtilisin rib bw.tif

1969{{snd}} Subtilisin (PDB file 1sbt {{cite journal |vauthors=Alden RA, Birktoft JJ, Kraut J, Robertus JD, Wright CS |title=Atomic coordinates for subtilisin BPN' (or novo) |year=1971 |journal=Biochem Biophys Res Commun |volume=45 |issue=2 |pages=337–44|doi=10.1016/0006-291X(71)90823-0|pmid=5160720 }}) was a second type of serine protease with a near-identical active site to the trypsin family of enzymes, but with a completely different overall fold. This gave the first view of convergent evolution at the atomic level. Later, an intensive mutational study on subtilisin documented the effects of all 19 other amino acids at each individual position.{{cite journal |vauthors=Wells J, Estell D |title=Subtilisin - an enzyme designed to be engineered |year=1988 |journal=Trends Biochem Sci |volume=13 |issue=8 |pages=291–297 |doi=10.1016/0968-0004(88)90121-1|pmid=3154281 }}

1970{{snd}} Lactate dehydrogenase

Image:BPTI ribbon 1bpi.jpg

1970{{snd}} Basic pancreatic trypsin inhibitor, or BPTI (PDB file 2pti{{cite journal |vauthors=Huber R, Kukla D, Ruhmann A, Epp O, Formanek H |title=The basic trypsin inhibitor of bovine pancreas. I. Structure analysis and conformation of the polypeptide chain |year=1970 |journal=Naturwissenschaften|volume=57 |pages=389–392 |doi=10.1038/231506a0 |pmid=4932997 |issue=5304|bibcode=1971Natur.231..506B |s2cid=4158731 }}), is a small, very stable protein that has been a highly productive model system for study of super-tight binding, disulfide bond (SS) formation, protein folding, molecular stability by amino-acid mutations or hydrogen-deuterium exchange, and fast local dynamics by NMR. Biologically, BPTI binds and inhibits trypsin while stored in the pancreas, allowing activation of protein digestion only after trypsin is released into the stomach.

Image:Rubredoxin Fe 2rxn rib.tif

1970{{snd}} Rubredoxin (PDB file 2rxn{{cite journal |vauthors=Herriott JR, Sieker LC, Jensen LH, Lovenberg W |title=Structure of rubredoxin: An X-ray study to 2.5Å resolution |year=1970 |journal=Journal of Molecular Biology |volume=50 |issue=2 |pages=391–402 |doi=10.1016/0022-2836(70)90200-7|pmid=5476919 }}) was the first redox structure solved, a minimalist protein with the iron bound by 4 Cys sidechains from 2 loops at the top of β hairpins. It diffracted to 1.2Å, enabling the first reciprocal-space refinement of a protein (4,5rxn{{cite journal |vauthors=Watenpaugh KD, Sieker LC, Jensen LH |title=Crystallographic refinement of rubredoxin at 1.2Å resolution |year=1980 |journal=Journal of Molecular Biology |volume=138 |issue=3 |pages=615–633 |doi=10.1016/s0022-2836(80)80020-9|pmid=7411618 }}). (NB: note that 4rxn was done without geometry restraints.) Archaeal rubredoxins account for many of the highest-resolution small structures in the PDB.

File:Insulin worm bw.jpg

File:Insulincrystals.jpg

1971{{snd}} Insulin (PDB file 1INS){{cite journal |vauthors=Blundell TL, Cutfield JF, Cutfield SM, Dodson EJ, Dodson GG, Hodgkin DC, Mercola DA, Vijayan M |title=Atomic positions in rhombohedral 2-zinc insulin crystals |year=1971 |journal=Nature |volume=231 |pages=506–511 |doi=10.1038/231506a0 |pmid=4932997 |issue=5304|bibcode=1971Natur.231..506B |s2cid=4158731 }} is a hormone central to the metabolism of sugar and fat storage, and important in human diseases such as obesity and diabetes. It is biophysically notable for its Zn binding, its equilibrium between monomer, dimer, and hexamer states, its ability to form crystals in vivo, and its synthesis as a longer "pro" form which is then cleaved to fold up as the active 2-chain, SS-linked monomer. Insulin was a success of NASA's crystal-growth program on the Space Shuttle, producing bulk preparations of very uniform tiny crystals for controlled dosage.

1971{{snd}} Staphylococcal nuclease

1971{{snd}} Cytochrome C

1974{{snd}} T4 phage lysozyme

1974{{snd}} Immunoglobulins

1975{{snd}} Cu,Zn Superoxide dismutase

1976{{snd}} Transfer RNA

File:TriosePhosphateIsomerase Ribbon pastel photo mat.png

1976{{snd}} Triose phosphate isomerase

• 1976{{snd}} Rhizopuspepsin
• 1976{{snd}} Endothiapepsin
• 1976{{snd}} Penicillopepsin

• 1978{{snd}} Icosahedral virus
• 1981{{snd}} Dickerson B-form DNA dodecamer
• 1981{{snd}} Crambin
• 1985{{snd}} Calmodulin
• 1985{{snd}} DNA polymerase

File:Photosynthetic Reaction Center Drawing.png

• 1985{{snd}} Photosynthetic reaction center: Pairs of bacteriochlorophylls (green) inside the membrane capture energy from sunlight, then traveling by many steps to become available at the heme groups (red) in the cytochrome-C module at the top. This was first crystal structure solved for a membrane protein, a milestone recognized by a Nobel Prize to Hartmut Michel, Hans Deisenhofer, and Robert Huber.

File:CAP-DNA 1cgp rib.tiff

• 1986{{snd}} Repressor/DNA interactions
• 1987{{snd}} Major histocompatibility complex
• 1987{{snd}} Ubiquitin
• 1987{{snd}} ROP protein
• 1989{{snd}} HIV-1 protease
• 1990{{snd}} Bacteriorhodopsin
• 1991{{snd}} GCN4 coiled coil
• 1991{{snd}} HIV-1 reverse transcriptase
• 1993{{snd}} Beta helix of Pectate lyase
• 1994{{snd}} Collagen
• 1994{{snd}} Barnase/barstar complex
• 1994{{snd}} F1 ATPase
• 1995{{snd}} Heterotrimeric G proteins
• 1996{{snd}} Green fluorescent protein
• 1996{{snd}} CDK/cyclin complex

File:064-Kinesin-3kin-composite.png

• 1996{{snd}} Kinesin motor protein
• 1997{{snd}} GroEL/ES chaperone
• 1997{{snd}} Nucleosome
• 1998{{snd}} Group I self-splicing intron

File:073-Topoisomerases Topo I-1a36.png

• 1998{{snd}} DNA topoisomerases perform the biologically important and necessary job of untangling DNA strands or helices that get entwined with each other or twisted too tightly during normal cellular processes such as the transcription of genetic information.
• 1998{{snd}} Tubulin alpha/beta dimer
• 1998{{snd}} Potassium channel
• 1998{{snd}} Holliday junction
• 2000{{snd}} Ribosomes are a central part of biology and biophysics, which first became accessible structurally in 2000

Image:121- RCSB Molecule-of-Month 70S 3-step Ribosome elongation.tif

• 2000{{snd}} AAA+ ATPase
• 2002{{snd}} Ankyrin repeats
• 2003{{snd}} TOP7 protein design
• 2004{{snd}} Cyanobacterial Circadian clock proteins
• 2004{{snd}} Riboswitch
• 2006{{snd}} Human exosome

Image:3sn6 G-coupled ribbon.png

• 2007{{snd}} G-protein-coupled receptor

File:Half-vault front.png

• 2009{{snd}} The vault particle is an intriguing new discovery of a large hollow particle common in cells, with several different suggestions for its possible biological function. The crystal structures (PDB files 2zuo, 2zv4, 2zv5{{cite journal |vauthors=Tanaka H, Kato K, Yamashita E, Sumizawa T, Zhou Y, Yau M, Iwasaki K, Yoshimura M, Tsukihara T |title=The Structure of Rat Liver Vault at 3.5 Angstrom Resolution |year=2009 |journal=Science |volume=323 |pages=384–388 |doi=10.1126/science.1164975 |pmid=19150846 |issue=5912|bibcode=2009Sci...323..384T |s2cid=2072790 }} and 4hl8{{cite journal |vauthors=Casanas A, Querol-Audi J, Guerra P, Pous J, Tanaka H, Tsukihara T, Verdaguer N, Fita I |title=New features of vault architecture and dynamics revealed by novel refinement using the deformable elastic network approach |year=2013 |journal=Acta Crystallographica |volume=D69 |pages=1054–1061 |pmid=23695250 |doi=10.1107/S0907444913004472 |issue=Pt 6|url=https://digital.csic.es/bitstream/10261/88208/1/New%20features.pdf |hdl=10261/88208 |hdl-access=free }}) show that each half of the vault is made up of 39 copies of a long 12-domain protein that swirl together to form the enclosure. Disorder at the very top and bottom ends suggests openings for possible access to the interior of the vault.

Image:4fby spline het.png

{{reflist}}

{{DEFAULTSORT:Biophysically important macromolecular crystal structures}}

Category:Structural biology

Macromolecular crystal structures

Macromolecular crystal structures

Macromolecular crystal structures