Introduction



Figure 1: Molecular strcture of Collagen


Collagen constitutes up to a third of all proteins in humans, making proteases involved in their remodelling an important area of study. Collagen is made of three polypeptide strands with a left-handed α-helical conformation. A distinctive feature of collagen is its regular repetitive arrangement of amino acids often following the sequence Gly-Pro-X or Gly-X-Hydroxyproline. Glycine is required at every third position; due to its small side-chain it helps stabilise the molecule and prevents steric hindrance. Three of these left-handed α-helices are twisted together in the quaternary structure, forming a right-handed ‘super-helix’.

Collagenases hydrolyse the peptide bonds in collagen molecules, and the most efficient include Collagenase G from Clostridium histolyticum. Ulrich et al. crystallised the structure of collagenase G to 2.55Å and combining their work with mutagenesis and enzymatic studies they were able to derive a full model of the ColG structure in addition to a model of bacterial collagenolysis. Clostridium histolyticum release Collagenase G as an exotoxin which helps facilitate the spread of gas gangrene in infections (figure 2). This occurs through targeting of the fibrous connective tissue between muscle cells. The bacteria thrive in anaerobic conditions, meaning once the infection starts to spread, more toxins may be realeased creating a serious health condition. Unwinding of the triple helices is driven my opening and closing of collagenase that we will be studying. But first let us examine the structure and unique architecture of the enzyme.




Figure 2: Patient with a gas gangrene infection,
a reults of Collagenase G in action!!