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Subtitle Barely Lethal


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Good morning. As a chemist in the Lindau physics meeting I decided to speak about basic properties of proteins.Of course, with some apologies to the chemists in the audience.So my focus is different from Hans Deisenhofer's talk but there is a useful overlap and I'm grateful for the arrangementof these 2 lectures in sequence because we both study proteins and mainly use x-ray crystallography.Well the title of my lecture which you see in the program maybe seem problematic because fitness for purpose is objectivebut beauty lies in the eyes of the beholder and the early protein models which we construct in the late '60's, early 70's,made from wire and screws are barely regarded, can barely be regarded as beautiful.But today we use computer graphics and tricks offered by this technology.But we must be aware of the fact that these models are metaphors yet still they are useful to derive molecular propertiesand plan new experiments. And if you want then be pleased by their beauty.Now why do we study proteins.Now proteins are the product of a complex series of transcription and translation with enormous increase in complexity.The genome is simple, the proteome complex. Yet the proteome decides about life phenomena.A beautiful illustration of that you see here, the mature butterfly and its larva share the same genomebut they are as different as you can imagine. So what are proteins.A few basic facts about their chemistry. They have a defined amino acid sequence.There are 20 natural amino acids of different stereochemistry and electrostatic properties.They are linked by amide peptide linkages.Now despite their construction from often ten thousands of atoms, they have defined structures.They are synthesised as unfolded structure-less chains and then in a sequence of hierarchical events of structure formationthey form via secondary structures, tertiary structures, the final quarternary structure which is the functional protein.We now talk about models, then it is quite obvious that the structures became transparentonly after very substantial simplification, this is an all atom model of a large protein with about 70,000 atoms,totally in-transparent.So we have to simplify it by just drawing out the polypeptide chain indicating the secondary structures, the helixes,the beta strands.So we can have surface representations to explore the binding potential of the proteinand this is the most simplified representation of this 28 sub unit aggregate.Just indicating the arrangement of the sub unit, the architecture.Now we use metaphors as I said already to describe protein structures, so these are propeller structures,there are 6 bladed or 5 bladed propellers.There are barrels with a remarkable similarity to the Castel del Monte in Apulia which share both the moleculeand the architect shares the 8 fold rotational symmetry.Strict of course in the case of the human construction and somewhat distorted in the real molecule.Now how do we know, Hans mentioned already there are 3 major techniques, crystallography, the working horse of structural biology.There is electron microscopy which is able to provide views usually at low resolution of very large molecular aggregates.Now what we often do now is disassemble these aggregates, separate the components, crystallise them,look at them at high resolution and then model back the large complex structure,the atomic resolution by fitting the atomic structuresinto the envelop given by electron microscopy and that is NMR which has the advantageof analysing protein structure resolution, all be it usually of small or medium sized proteins.Now Hans mentioned the major breakthroughs in structural biology but of course it began,crystallography began earlier with Ran




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