Since the precise 3D structure of a protein is essential for its function, misfolding can result in significant downstream consequences. If this misfolding occurs to an enzyme, oftentimes the catalytic reaction can no longer take place, leading to substrate accumulation to toxic levels and subsequent cellular dysfunction.
There are many reasons why enzymes misfold. The most obvious is a genetic mutation in which a change to the amino acid sequence leads to an incorrect folding pattern. However, there are other causes of misfolding that can affect even wildtype enzymes, including states that increase cellular stress such as aging and inflammation.
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