The Binding of AZT polymerase to human DNA polymerase beta

In this image, human DNA polymerase beta is shown with a double strand of DNA (seven base pairs) at its catalytic site.  The DNA lies in a cleft in the enzyme in which the catalytic site is located.

First, highlight the the two chains of the DNA: Chain 1  [ On Off ] chain 2 [ On  Off ].  You can rotate the molecule any time here   [Rotate On  Rotate Off  ]. Or you can drag it with your left button and mouse.

The crystalline protein was soaked in azidothymidine (AZT) which is a substrate that binds at the nucleotide binding site of the polymerase before being added to the 3' end of a DNA strand. To show this site, highlight the AZT [ On .  Off ]

The interaction of the protein with the DNA and the AZT may be seen better if you convert the enzyme to strands  or ribbons   or space-fill  

Let's look at the active site of the enzyme. First, highlight residues 190 and 192 which are aspartic acid residues involved in catalysis [ Active site carboxylate residues - space fill: Asp 190 192  . Active site carboxylate residues - ribbons: Asp 190 192   Active site carboxylate residues - strands: Asp 190 192  ] These amino acids interact with the nucleotide to be added to the 3' end of one of the DNA chains, in this case it is AZT. Also involved in catalysis are tyrosine 271 and threonine 273. Highlight residues 271-273 here [Residues 271-273 - space fill:  . Residues 271-273 - ribbons . Residues 271-273 - strands .] This part of the enzyme interacts with the sugar of the nucleotide to be added. Aspartate 256 is also involved in catalysis at the active site [Space fill: Asp  256  . Ribbons: Asp  256  Strands: Asp  256  . ] This occurs via a catalytic metal ion  [Spacefill metal ion 6 ] The crystal strcuture also shows another metal ion associated with the nucleotide substrate [Spacefill metal ion 1 ].  [Rotate On  Rotate Off  ]

It may be useful to highlight the 5' ends of the T DNA chain  , the 3' end of this chain  , the 5' end of the P chain  and the 3' end of this chain 

You can also look at the alpha helices (purple) and the beta sheets of the polymerase enzyme here

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Protein  Database information is here (81C0)

© Dr Richard Hunt, University of South Carolina School of Medicine