Highest impact structures: Difference between revisions
| (16 intermediate revisions by 2 users not shown) | |||
| Line 11: | Line 11: | ||
This list is in chronological order. | This list is in chronological order. | ||
* '''1953 - [[DNA]] double helix''' (B form): Although Watson and Crick's model was theoretical | ===20th Century=== | ||
* '''1953 - [[DNA]] double helix''' (B form): Although Watson and Crick's model was not based on 3D crystallographic data, the fiber diffraction images obtained by Rosalind Franklin guided them in their hypotheses. The theoretical model they arrived at was essentially correct, and for the first time explained the ability of genes to be faithfully copied during cell division. It was not confirmed by atomic resolution X-ray crystallography until 1973, using RNA dinucleotide crystals. A full turn of B form DNA was not solved until 1980 (cf. [[1bna]]), 27 years after Watson and Crick's model. More: click on DNA at the [http://atlas.molviz.org Atlas of Macromolecules] | |||
* '''1958 - [[Myoglobin]]''': As the first protein structure that was determined, it is hard to exaggerate its impact. Before this structure, proteins were widely believed to be colloidal, and protein crystals were expected to contain highly symmetrical structures. The irregular fold of myoglobin (see photo of an early low-resolution model at [[Nobel Prizes for 3D Molecular Structure]]) was a huge surprise. | * '''1958 - [[Myoglobin]]''': As the first protein structure that was determined, it is hard to exaggerate its impact. Before this structure, proteins were widely believed to be colloidal, and protein crystals were expected to contain highly symmetrical structures. The irregular fold of myoglobin (see photo of an early low-resolution model at [[Nobel Prizes for 3D Molecular Structure]]) was a huge surprise. | ||
| Line 18: | Line 20: | ||
Lysozymes: Model Enzymes in Biochemistry and Biology By Pierre Jollès, Birkhäuser, 1996 | Lysozymes: Model Enzymes in Biochemistry and Biology By Pierre Jollès, Birkhäuser, 1996 | ||
ISBN 3764351217</ref> An inhibitor-bound structure determined in the same year showed the non-covalent interactions between binding cleft and the ligand. Lysozyme is a model enzyme for studying crystallization, the impact of crystal packing on structure, catalytic activity in the crystalline state, and the consequences of mutations on structure and activity. (See [[lysozyme]].) | ISBN 3764351217</ref> An inhibitor-bound structure determined in the same year showed the non-covalent interactions between binding cleft and the ligand. Lysozyme is a model enzyme for studying crystallization, the impact of crystal packing on structure, catalytic activity in the crystalline state, and the consequences of mutations on structure and activity. (See [[lysozyme]].) | ||
* '''1969 - Insulin''': The [[Insulin|insulin structure]] was solved in 1969 by Dorothy Hodgkin, a pioneering X-ray crystallographer who had previously won the Nobel prize for her work on vitamin B12<ref name="hodgkin">https://www.nobelprize.org/prizes/chemistry/1964/hodgkin/biographical/</ref>. Insulin itself is used as a live-saving drug to treat type 1 diabetes. Using the structure of hexameric insulin (the storage form) as guidance, variations of insulin were developed that are fast-acting or slow-acting. | |||
* '''1970 - Deoxy-hemoglobin''': M. Perutz' second hemoglobin structure proved to be at least as important as the first, published two years earlier, as it demonstrated that a protein can have several conformations, and that its physiological role depends on how it changes from one to the other. (See [[Hemoglobin]].) | * '''1970 - Deoxy-hemoglobin''': M. Perutz' second hemoglobin structure proved to be at least as important as the first, published two years earlier, as it demonstrated that a protein can have several conformations, and that its physiological role depends on how it changes from one to the other. (See [[Hemoglobin]].) | ||
| Line 28: | Line 32: | ||
* '''1987 - [[Major_Histocompatibility_Complex_Class_I | Major histocompatibility complex class I]]''': Created a paradigm shift in cellular immunology by explaining how MHC is involved in presenting hidden intracellular proteins to T lymphocytes. During the decade prior to this structure, this was a constantly debated but very murky mystery. | * '''1987 - [[Major_Histocompatibility_Complex_Class_I | Major histocompatibility complex class I]]''': Created a paradigm shift in cellular immunology by explaining how MHC is involved in presenting hidden intracellular proteins to T lymphocytes. During the decade prior to this structure, this was a constantly debated but very murky mystery. | ||
===21st Century=== | |||
* '''2000 - [[Ribosome]]''': This structure surprised almost everyone by showing that peptidyl transferase is a ribozyme, rather than a protein enzyme. It won the [[Nobel_Prizes_for_3D_Molecular_Structure#Twenty-First_Century|2009 Nobel Prize in Chemistry]]. | * '''2000 - [[Ribosome]]''': This structure surprised almost everyone by showing that peptidyl transferase is a ribozyme, rather than a protein enzyme. It won the [[Nobel_Prizes_for_3D_Molecular_Structure#Twenty-First_Century|2009 Nobel Prize in Chemistry]]. | ||
* '''2007 and 2011 - [[G protein-coupled receptor]]''': In 2007 the structure of the first ligand-activated G protein-coupled receptor and in 2011 the first activated G protein-coupled receptor bound to its G protein. This is a large class of proteins that have great importance as targets for drug development; it is estimated that 4% of the human genome devoted to protein coding encodes this class of proteins. The determination of the structures lead to Brian Kobilika sharing the [[Nobel_Prizes_for_3D_Molecular_Structure#Twenty-First_Century|2012 Nobel Prize in Chemistry]] | * '''2007 and 2011 - [[G protein-coupled receptor]]''': In 2007 the structure of the first ligand-activated G protein-coupled receptor and in 2011 the first activated G protein-coupled receptor bound to its G protein. This is a large class of proteins that have great importance as targets for drug development; it is estimated that 4% of the human genome devoted to protein coding encodes this class of proteins. The determination of the structures lead to Brian Kobilika sharing the [[Nobel_Prizes_for_3D_Molecular_Structure#Twenty-First_Century|2012 Nobel Prize in Chemistry]] | ||
<!-- | |||
* '''2019 - Cytochrome nanowires''': [[6ef8]] was the first structure of an electrically-conductive bacterial protein nanowire, confirmed by [[6nef]]. Such nanowires appear to be important in global carbon and metal redox phenomena in anoxic soils and sediments, and have many possible applications<ref>PMID: 24863901</ref><ref>PMID:27801905</ref><ref>PMID: 31240257</ref>. Prior to these [[cryo-EM]] structures, it had been believed for over a decade that nanowires were type IV pili assembled from pilA<ref>PMID: 30951668</ref>. These structures surprisingly revealed nanowires as polymers of 6-heme C-type cytochromes, which called this belief into question. The unexpected protein making up these nanowires was determined from the cryo-EM density map. This is an unusual case in which the protein making up an extensively-studied organelle was not known prior to solving its atomic-level structure. | |||
--> | |||
==Structures Saving The Most Lives== | ==Structures Saving The Most Lives== | ||
| Line 36: | Line 46: | ||
Structures of the following molecules were used in Structure-based drug design, and the resulting drugs have saved large numbers of lives. | Structures of the following molecules were used in Structure-based drug design, and the resulting drugs have saved large numbers of lives. | ||
* The [[Insulin| | * The [[Insulin|'''insulin''' structure]] was solved in 1969 by Dorothy Hodgkin, a pioneering X-ray crystallographer who had previously won the Nobel prize for her work on vitamin B12<ref name="hodgkin"/>. Insulin itself is used as a life-saving drug to treat type 1 diabetes. Using the structure of hexameric insulin (the storage form) as guidance, variations of insulin were developed that are fast-acting or slow-acting. | ||
* [[Avian Influenza Neuraminidase, Tamiflu and Relenza|Influenza virus neuraminidase structure]] was used in designing the neuraminidase inhibitors [[Avian Influenza Neuraminidase, Tamiflu and Relenza|oseltamivir (Tamiflu®) and zanamivir (Relenza®)]]. Roche, the manufacturer of Tamiflu, estimates that 50 million people have been treated with this drug<ref>[http://www.roche.com/med-cor-2007-04-26 Roche update on Tamiflu for pandemic influenza preparedness], Media Release, April 26, 2007.</ref>. The [http://en.wikipedia.org/wiki/Cochrane_Collaboration Cochrane Collaboration] concluded that neuriminidase inhibitors "are effective in preventing and treating the symptoms and complications of influenza"<ref>[http://mrw.interscience.wiley.com/cochrane/clsysrev/articles/CD001265/frame.html Neuraminidase inhibitors for preventing and treating influenza in healthy adults], T. Jefferson ''et al.'', Cochrane Database of Systematic Reviews, Issue 4, 2008. DOI [http://dx.doi.org/10.1002/14651858.CD001265.pub2 10.1002/14651858.CD001265.pub2]</ref>. Influenza kills hundreds of thousands of people annually<ref>[http://en.wikipedia.org/wiki/Influenza Influenza] in Wikipedia.</ref>, including 40,000 in the United States<ref>[http://aje.oxfordjournals.org/cgi/content/full/163/2/181 Mortality due to Influenza in the United States—An Annualized Regression Approach Using Multiple-Cause Mortality Data], J. Dushoff ''et al.'', Am. J. Epidemiol. 163:181-7, 2006.</ref>. While it is difficult to estimate accurately the number of lives saved by these drugs, the number seems likely to be very large. | * [[Avian Influenza Neuraminidase, Tamiflu and Relenza|'''Influenza virus neuraminidase''' structure]] was used in designing the neuraminidase inhibitors [[Avian Influenza Neuraminidase, Tamiflu and Relenza|oseltamivir (Tamiflu®) and zanamivir (Relenza®)]]. Roche, the manufacturer of Tamiflu, estimates that 50 million people have been treated with this drug<ref>[http://www.roche.com/med-cor-2007-04-26 Roche update on Tamiflu for pandemic influenza preparedness], Media Release, April 26, 2007.</ref>. The [http://en.wikipedia.org/wiki/Cochrane_Collaboration Cochrane Collaboration] concluded that neuriminidase inhibitors "are effective in preventing and treating the symptoms and complications of influenza"<ref>[http://mrw.interscience.wiley.com/cochrane/clsysrev/articles/CD001265/frame.html Neuraminidase inhibitors for preventing and treating influenza in healthy adults], T. Jefferson ''et al.'', Cochrane Database of Systematic Reviews, Issue 4, 2008. DOI [http://dx.doi.org/10.1002/14651858.CD001265.pub2 10.1002/14651858.CD001265.pub2]</ref>. Influenza kills hundreds of thousands of people annually<ref>[http://en.wikipedia.org/wiki/Influenza Influenza] in Wikipedia.</ref>, including 40,000 in the United States<ref>[http://aje.oxfordjournals.org/cgi/content/full/163/2/181 Mortality due to Influenza in the United States—An Annualized Regression Approach Using Multiple-Cause Mortality Data], J. Dushoff ''et al.'', Am. J. Epidemiol. 163:181-7, 2006.</ref>. While it is difficult to estimate accurately the number of lives saved by these drugs, the number seems likely to be very large. | ||
* [[HIV-1_protease|HIV protease structure]] was used in designing [http://en.wikipedia.org/wiki/Protease_inhibitor_(pharmacology) anti-retroviral protease inhibitors] that, as a component of [http://en.wikipedia.org/wiki/Antiretroviral_drug Highly Active Anti-Retroviral Therapy (HAART)], have added many high-quality years to the lives of HIV infected individuals. While HAART greatly extends life in HIV infected patients, it is not a cure, and these patients may eventually succumb to AIDS. For more, please see [[User:Eric_Martz/Molecular_Playground/HIVDrug|AIDS Before Protease Inhibitors & HIV Protease Inhibitors: A Breakthrough]]. | * [[HIV-1_protease|'''HIV protease''' structure]] was used in designing [http://en.wikipedia.org/wiki/Protease_inhibitor_(pharmacology) anti-retroviral protease inhibitors] that, as a component of [http://en.wikipedia.org/wiki/Antiretroviral_drug Highly Active Anti-Retroviral Therapy (HAART)], have added many high-quality years to the lives of HIV infected individuals. While HAART greatly extends life in HIV infected patients, it is not a cure, and these patients may eventually succumb to AIDS. For more, please see [[User:Eric_Martz/Molecular_Playground/HIVDrug|AIDS Before Protease Inhibitors & HIV Protease Inhibitors: A Breakthrough]]. | ||
==See Also== | ==See Also== | ||
| Line 48: | Line 58: | ||
*[http://www.umass.edu/microbio/rasmol/1st_xtls.htm Earliest Solutions for Macromolecular Crystal Structures] | *[http://www.umass.edu/microbio/rasmol/1st_xtls.htm Earliest Solutions for Macromolecular Crystal Structures] | ||
*[[Personal favorites]] | *[[Personal favorites]] | ||
* [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3945011/ Biophysical Highlights, Richardson and Richardson] | |||
*[http://www.molecularstructure.org/ Structural Biology Rankings] ranks 3D structures according to their popularity among scientists and citation count. | *[http://www.molecularstructure.org/ Structural Biology Rankings] ranks 3D structures according to their popularity among scientists and citation count. | ||