1. Matrix Metalloproteinase is an enzyme that aids in degrading extracellular pr
ID: 143485 • Letter: 1
Question
1. Matrix Metalloproteinase is an enzyme that aids in degrading extracellular proteins in order aid in cell proliferation, cell migration, or angiogenesis (formation of new blood vessels). Different homologs are found are able to degrade various substrates within tissues. Shown below is a segment of an amino acid sequence alignment of the active site of various homologs: in MMP-1 (collagenases) MMP-2 (gelatinases) MMP-3 (stromelysins) MMP-11 (stromelysins) MMP-12 (collagenases) MMP-19 (collagenases) HRVAAHELGHSLGLSHSTDI FLVALHELGHTLGLFHSANT FLVAAHEIGHSLGLFHTANT LQVAIHEFGHVLGLQHTTAA NLFTAVHEFGHSLGLAHSSDG RILAAHEVGHALGLGHTRYS a. Based on this alignment, write the sequence motif (e.g. PxxxRxG) that appears to be essential for structure and/or function. Note: there is more than one correct answer depending on the arbitrary threshold you use decide conserved vs. not conserved The majority of MMP substrates have high concentrations of glycine, proline, and alanine. Consider where these essential residues would fall on an alpha helix. How might the motif you determined facilitate bonding with substrates? b.Explanation / Answer
(a) To find the sequence motif essential for the structure/function of the enzyme we find the common sequence portion that is conserved in all of the enzymes' sequences. On comparing it can be seen that the sequence motif is HEXXHXXGXXH where X is any other Amino acid residue.
(b) First thing that should be known is that the substrate for these enzymes is Zinc ion ('metallo proteinase'). Glycine, Proline and Alanine are all hydrophobic acids and should lie on the side of the alpha-helix, away from the substrate binding site.
The Histidine (H) and Glutamate (E) are charged amino-acids and are present in the sequence motif of these enzymes. These charged amino-acids facilitate as acid/base for Zinc ion during catalysis. In this way the motif facilitates bonding with the substrates.
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