[M.D.]

Why is it so important to discover shape of a molecule?

As far as I know, first theory that molecules are shaped was proposed by an  architect intreseted in chemistry and later confirmed by x-ray crystallography.

Focus of my question is mainly on determing the shape of proteins in biochemistry, but can be generalized and asked why is it so important in the first place.

I know it is no easy task to answer it, but I'll hope to get help.

thanks

[Yggdrasil]

The structure of proteins is an important topic in biochemistry because the structure of proteins allows them to perform their specific functions in the cell.  From a purely chemical perspective, proteins are simple; they are polymers which contain only 20 different amino acids in a specific order.  What allows these simple polymers to catalyze reactions, interact with components of the cell, and perform a variety of other functions in the cell is the fact that they fold into a specific shape.  The shape of the protein creates specific pockets and binding surfaces where substrates or interaction partners can bind.

Hemoglobin is a good example of how the structure of a protein is essential to its function.  An alpha helix in hemoglobin (the F-helix) is positioned in such a way that when oxygen binds to hemoglobin, the iron in hemoglobin pulls a histadine on the F-helix which subtly changes the structure of hemoglobin.  This change is structure is communicated to the other subunits of hemoglobin which aids in the cooperative binding.

For more examples of how protein structure defines function, see the molecule of the month feature at the protein databank (http://www.rcsb.org/pdb/static.do?p=education_discussion/molecule_of_the_month/index.html), an open access database containing all of the solved protein structures.

So, why do biochemists study protein structure?  First, by obtaining structures of proteins, we can help determine the exact mechanism of how they function and obtain atomic-level details of the interactions that they mediate (for example, what amino acids interact when two proteins bind eachother).  This information can aid in the design of drugs to inhibit specific reactions or interactions within the cell (for example, a structure of an enzyme from HIV can help design drugs to fight AIDS).  Also, studying protein structure can generate basic knowledge about protein folding.  This knowledge can aid in many fields including the creation of designer proteins (for example, researchers have created biosensors for a variety of molecuels) and a better understanding of diseases related to protein misfolding (for example, Alzheimer's disease).

[M.D.]

The structure of proteins is an important topic in biochemistry because the structure of proteins allows them to perform their specific functions in the cell. 

.

So, why do biochemists study protein structure? 

First of all, thank you for a quick response! It cleared out some of the things.

My definition would be that shape of a protein makes some atoms closer to each other (both of the protein itself or some substrate) so that they are placed on a distance that is close enough to make bonds or any other type of chemical reaction.

Would this be acceptable?

I'm trying for a way how can a protein shape help me in learning biochemistry, instead of making it difficult. Ok, I'll memorize that chemoglobine has 4 subunits, that has a globular shape, etc. but how can that help me to understand it better? Obviously, that has a point and I'm not very proud that I can't see it in this moment...

[Yggdrasil]

My definition would be that shape of a protein makes some atoms closer to each other (both of the protein itself or some substrate) so that they are placed on a distance that is close enough to make bonds or any other type of chemical reaction.

Would this be acceptable?

Yes, that's a decent explanation.

I'm trying for a way how can a protein shape help me in learning biochemistry, instead of making it difficult. Ok, I'll memorize that chemoglobine has 4 subunits, that has a globular shape, etc. but how can that help me to understand it better? Obviously, that has a point and I'm not very proud that I can't see it in this moment...

The way I see it, structural biology (the analysis of protein structures) helps to connect the biology of proteins to their chemistry.  From biology, we know the function of proteins.  For example, we know that trypsin, a digestive enzyme in the stomach, aids digestion by cleaving polypeptide chains.  But, how does the trypsin accomplish this task?  What chemistry is involved and what is the mechanism?  To answer these questions, one must look at the structure of trypsin.

Genetic and biochemical studies of trypsin showed that a serine, a histadine, and an aspartate were important for its ability to catalyze the cleavage of peptides.  A structure of trypsin helped to make sense of these results.  The structure of trypsin (see http://www.rcsb.org/pdb/static.do?p=education_discussion/molecule_of_the_month/pdb46_3.html) showed that the serine, histadine, and aspartate were arranged with such a geometry to allow the serine to catalyze the cleavage of peptides.  The environment around the aspartate (notably the histadine) helps to raise the pKa of the aspartate such that it deprotonates the neighboring serine, creating an oxyanion.  It is this oxyanion that allows trypsin to covalently bond with a peptide, breaking the bond between amino acids of the peptide.  So, the structure of trypsin tells us why the serine, aspartate, and histadine are important to trypsin's function, and it lets us understand how trypsin catalyzes its chemical reaction in terms of simple concepts from organic chemistry.

So, in terms of learning biochemistry, structural information will give you a better understanding of the details about how biological macromolecules perform their functions.  Not all of the information will be completely relevant (for example, by no means should you try to memorize the entire structure of a protein), but you will see some important features (such as the arrangement of the serine, aspartate, and histadine in trypsin) that will help you better understand how these proteins perform their functions within the cell.