How dose a change in the sequence of nucleotides in a strand of DNA might cause a protein to malfunction

By central dogma, we know that primary structure of the protein is synthesized on the basis of nucleotide sequence of the DNA.

First, the nucleotide sequence is decoded into mRNA which then provides the codon sequence which finally decide the sequence of amino acids in any polypeptide chains.

This amino acid sequence plays an important role in determining the inter and intra polypeptide chain interactions which determine the shape of the protein.

The shape or three dimensional structure of a protein is very important for its proper functioning.

Now, change in nucleotide sequence of the DNA can alter the amino acid sequence of the polypeptide chain which may alter the interactions required for proper folding of the protein. Thus it can result into the formation of mal-functional or non-functional protein.

For example, change in only one nucleotide in DNA leads to the development of sickle cell anemia due to the change in the shape of protein.