Beta-lactam antibiotics were initially able to effectively prevent MRSA colonization by inhibiting the synthesis of the cell wall and inducing osmotic lysis. However, as mentioned previously, the bacteria began to develop resistance to this class of antibiotics. At approximately the same time that MRSA strains began to show this antibiotic resistance, a novel gene called mecA began to surface throughout various strains. This gene, and its accompanying cassette, encodes for a modified PBP that is directly correlated with antibiotic resistance. The enzyme, now recognized as PBP2a, catalyzes the transpeptidation reaction necessary to synthesize the cell wall like other PBPs but has a unique structure. In x-ray crystallographic models of the apo-PBP2a structure, a beta3-beta4 loop motif is located directly above the active site. Active site structural comparisons between PBP2a and other PBPs revealed that the active site was conserved across all proteins and maintained the same catalytic mechanism. These findings indicate that the active site of PBP2a does not determine antibiotic resistance, but rather that the inability of antibiotics to reach the active site from the obstruction of the novel beta3-beta4 loop. If beta-lactam antibiotics were able to bind and inactive other members of the PBP family through the previously mentioned acylation reaction, it would fail to affect PBP2a. As a result, the novel protein would continue to catalyze the formation of the bacterial cell wall and would not lyse. This restricting loop poses a significant challenge for future antibiotic development as not only does it block beta-lactam antibiotics, but it also prevents other categories of antibiotics from accessing the active site.