http://pdbe.org/quips Quips are interactive stories about Quite Interesting PDB Structures. en-gb Copyright: (C) European Molecular Biology Laboratory 2004-2008 Wed 22 Sep 2011 16:28 Status pdbehelp@ebi.ac.uk Saturday Sunday http://www.ebi.ac.uk/pdbe/docs_dev/logos/images/RGB/PDBe-logo-RGB_2013.png http://www.ebi.ac.uk/pdbe/ 50 50 Protein Data Bank Europe http://pdbe.org/quips?story=chopstick What do transcription factors and the Karate Kid have in common? Find out in this Quips article exploring how bZip domains dimerise and bind to DNA. http://pdbe.org/quips?story=AChE Acetylcholinesterase is an enzyme that is an essential component of the nervous system. It is a target of chemical weapons, snake venoms and also anti-dementia drugs. Find out how it works, and how it is inhibited, in this Quips article. http://pdbe.org/quips?story=Cystatin Protein residues in unfavourable regions of the Ramachandran plot merit close inspection. It may mean that the model was built incorrectly, but in the case of the cystatin family, a Ramachandran outlier is essential for function. However, it's also the protein's Achilles' heel and can result in the protein adopting a pathogenic form which leads to dementia, haemorrhage and death. http://pdbe.org/quips?story=Transformer Can a single sequence of amino acids form more than one three-dimensional fold to achieve different physiological functions? The bacterial transcription factor RfaH has been shown to undergo extreme conformational transformation. It is able to switch between two completely different secondary and tertiary structures, each with a specific physiological function. You can explore this remarkable transformer protein in our latest interactive Quips article. http://pdbe.org/quips?story=avidin Avidin is a biotin-binding protein produced by birds, reptiles and amphibians and is deposited in their eggs. Avidin binds to biotin (also known as vitamin H) with an egg-stremely high degree of affinity and specificity making the system a very useful tool in biotechnology and medicine. You can explore the structural basis for this remarkable affinity in our latest interactive Quips article. http://pdbe.org/quips?story=CXI Complex I plays a key role in cellular energy production. For the first time, the structure of complex I, the first enzyme of the respiratory chain, has been determined in its entirety. This structure reveals the organisation of the 16 subunits and provides clues as to how this enzyme works. Our complex I Quips helps you explore the structure. http://pdbe.org/quips?story=insulin Insulin is a peptide hormone, produced by beta cells of the pancreas, and is central to regulating carbohydrate and fat metabolism in the body. Failure to control insulin levels can result in high blood sugar and diabetes, which affects around 300 million people worldwide. Insulin was one of the earliest protein structures to be solved. It was studied by Nobel Prize-winning crystallographer Dorothy Hodgkin. She and her team (*) worked extensively on this from the 1930s, finally determining the structure of porcine insulin (which is only one amino acid different compared to the human form) in 1969. More than forty years after the structure of insulin was first determined, and after four Nobel Prizes, insulin continues to be the subject of much research. You can explore the three dimensional structure of this important protein in our latest installment of Quips. (*) Guy Dodson sadly passed away on Christmas Eve. Guy began his studies with Dorothy Hodgkin in Oxford where he was closely involved with the crystallographic structure determination of insulin. He is a co-author of last week's Nature paper that describes the structure of insulin bound to its receptor (PDB entries 3w11, 3w12, 3w13 and 3w14). http://pdbe.org/quips?story=B2AR Today, Nobel Laureates Robert J. Lefkowitz and Brian K. Kobilka take center stage in Stockholm where they will receive their Nobel Prize Medals for their studies of G-protein–coupled receptors (GPCRs). To mark this occasion we have written a special Quips article which explores the Nobel Prize winning structure of B2AR bound to its G-protein. GPCRs are signalling proteins which enable cells to communicate with each other and the surrounding environment. They provide the molecular framework and mechanism for the transmission of a wide variety of signals over the cell membrane, between cells and over long distances in the body. In this quips you will learn how the structure of B2AR bound to its G-protein helped explain how binding of a small molecule on one face of B2AR activates the G-protein. http://pdbe.org/quips?story=Glue Candida albicans, the fungus that causes candidiasis, uses proteins called adhesins to stick to its host in order to infect it. The structure of a Candida adhesin shows that it is similar to bacterial adhesins, but its adhesive properties are very different. The structure reveals how it can stick to lots of different proteins and why it has a strong preference for grabbing their C-terminal ends. http://pdbe.org/quips?story=TolC In order to expel toxic chemicals from the cell, Gram negative bacteria must export them across both the inner and outer membranes and the periplasm in between them. In this Quips, find out how the TolC duct is built to convey these chemicals across the periplasm and outer membrane, and how it prevents leakage back into the periplasm. http://pdbe.org/quips?story=Sunhats Plants suffer from DNA damage caused by ultraviolet light in the same way that humans do. Unlike us though, they can’t put on a sunhat to avoid the sun’s rays. This Quips explains how plants sense UV-B light and turn on a suite of genes to protect their DNA against its deleterious effects. http://pdbe.org/quips?story=LordCBL E3 ubiquitin ligase is responsible for flagging proteins for degradation by transferring ubiquitin from a donor protein onto the molecule to be degraded. It is activated by phosphorylation of a tyrosine which promotes a huge conformational change, swinging its RING domain 180 degrees to put the enzyme's two substrates in proximity. http://pdbe.org/quips?story=BetaClamp DNA polymerases use a protein called the beta-clamp to hold onto a DNA strand as they replicate it. A sequence of amino acids at the C-terminus of the polymerase is responsible for this interaction and short peptides inspired by this sequence competitively inhibit the interaction. These peptides have enabled the identification of small molecule inhibitors which may lead to new antibiotics in the future. http://pdbe.org/quips?story=XmasFactor Christmas Factor is a serine protease that is part of the blood-clotting cascade, an important pathway responsible for preventing blood loss. The protein is named after a patient whose gene had a mutation (Cys->Ser) that causes a form of haemophilia. The structures of Christmas Factor in the PDB shed light on its function and activation mechanism and also explain the deleterious effect of the mutation responsible for Christmas Disease. http://pdbe.org/quips?story=T4tail Bacteriophage T4 is a fascinating macromolecular machine that infects E. coli to have the bacterium make more copies of T4. This story describes the remarkable needle-like structure of the lower part of the T4 "leg". It is thought that the head domains of these legs bind receptors on the bacterial outer membrane surface and thereby firmly attach the virus to its host. http://pdbe.org/quips?story=Phaser This episode of Quips looks back at the first crystal structure that was solved with the program Phaser and also tries to explain in (almost) layman's terms how Molecular Replacement works. The accompanying mini-tutorial shows you how to do multiple structure superimposition using PDBeFold (SSM). http://pdbe.org/quips?story=Autotaxin This Quips story describes the medical significance, 3D structure and atomic details of the function of autotaxins. It was developed with Anastasis Perrakis and Wouter Moolenaar who have authored a recent review on autotaxins. http://pdbe.org/quips?story=ATPexchange ATP, the enerygy currency of the cell, is minted by mitochondria. This edition of Quips describes the structure of a key carrier protein embedded in mitochondrial membrane, which carries ADP into and ATP out of the organelle. http://pdbe.org/quips?story=MHCstory PDBe are marking this annotation milestone by describing the workings of chicken MHC protein present in the 10,000th entry. http://pdbe.org/quips?story=NGFstory This Quips episode describes the molecule that guides development of our brain. http://pdbe.org/quips?story=PantonValentine Not all things Valentine are sweet, soft or pink! Read on about the Panton-Valentine leukocodin complex in this inaugural edition of Quips to figure out why!