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== Cell Wall Structure==
 
The bacterial cell wall is crucial for maintaining the structural integrity of bacteria and protects bacteria from osmotic stress and toxic compounds. The cell wall is composed of peptidoglycan (Figure 2) and in Gram positive bacterial species (e.g., S. aureus) is many layers thick, while in Gram negative bacterial species (e.g., Escherichia coli) is only a few layers thick. The difference in the number of peptidoglycan layers accounts for the differential staining of these two groups of organisms.  . Peptidoglycan consists of a carbohydrate portion: alternating residues of N-acetylmuranic Acid (NAM) and N-acetylglucosamine (NAG) that polymerize to form long chains, and a protein portion: a pentapeptide chain that terminates with two D-alanine (D-Ala) residues. The pentapeptide chains are covalently bound to each NAM residue Rows of peptidoglycan are cross-linked together with pentaglycine chains to form a "mesh-like" structure. This cross-linking reaction is catalyzed by TPs.  
== Cell Wall Structure ==
The bacterial cell wall is crucial for maintaining the structural integrity of bacteria and protects bacteria from osmotic stress and toxic compounds. The cell wall is composed of peptidoglycan (Figure 2 ) and in Gram positive bacterial species (e.g., S. aureus) is many layers thick, while in Gram negative bacterial species (e.g., Escherichia coli) is only a few layers thick. The difference in the number of peptidoglycan layers accounts for the differential staining of these two groups of organisms.  . Peptidoglycan consists of a carbohydrate portion: alternating residues of N-acetylmuranic Acid (NAM) and N-acetylglucosamine (NAG) that polymerize to form long chains, and a protein portion: a pentapeptide chain that terminates with two D-alanine (D-Ala) residues. The pentapeptide chains are covalently bound to each NAM residue Rows of peptidoglycan are cross-linked together with pentaglycine chains to form a "mesh-like" structure. This cross-linking reaction is catalyzed by TPs.  


[[Image:Cell Wall 7 30 2013.jpg|thumb|alt= Alt text| Figure 1. A.Bacterial Cell Wall  B.Peptidoglycan with D-Ala-D-Ala substrate |550px]]  
[[Image:Cell Wall 7 30 2013.jpg|thumb|alt= Alt text| Figure 1. A.Bacterial Cell Wall  B.Peptidoglycan with D-Ala-D-Ala substrate |550px]]  
== Structure of a Resistant Transpeptidase ==
Methicillin resistant Staphylococcus aureus (MRSA) is resistant to all β-lactams because it acquires an alternative PBP, PBP2a, that is not bound or inhibited by any β-lactams. PBP2a is composed of two domains: a <font color='orange'><b>non-penicillin binding domain </b><scene name='36/365380/4dki_cartoon/25'>(NPB) </scene></font> and a <font color='dodgerblue'><b>transpeptidase <scene name='36/365380/4dki_cartoon/26'>(TP)</scene> binding domain </b></font>. The NBP domain of PBP2a is anchored in the cell membrane, while the TP domain “sits” in the periplasm with its active site facing the inner surface of the cell wall. The active site contains <scene name='36/365380/Ser403/19'>a serine residue at position 403 (ser403)</scene> which catalyzes the cross-linking of the peptidoglycan rows with pentaglycine cross-links.




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[[Image:Structures on penicillin and b lactam.jpg|thumb|alt= Alt text|Figure 3. Mechanism of action of β-lactams. A. Structure of a β-lactam (penicillin) showing the amide, carboxyl, and β-lactam ring groups β-lactam ring groups. B. Structure of the D-Ala-D-Ala substrate. C. Overlay of the D-Ala-D-Ala substrate in red with penicillin demonstrating molecular mimicry.|550 px]]
[[Image:Structures on penicillin and b lactam.jpg|thumb|alt= Alt text|Figure 3. Mechanism of action of β-lactams. A. Structure of a β-lactam (penicillin) showing the amide, carboxyl, and β-lactam ring groups β-lactam ring groups. B. Structure of the D-Ala-D-Ala substrate. C. Overlay of the D-Ala-D-Ala substrate in red with penicillin demonstrating molecular mimicry.|550 px]]
== Structure of PBP2a, a B-lactam Resistant Transpeptidase==
Isolates of methicillin-resistant S. aureus (MRSA) are resistant to almost all currently available B-lactam because they have acquired an alternative PBP, PBP2a(encoded by the mecA gene), that is neither bound nor inhibited by B-lactams. PBP2a is composed of two domains:a a <font color='orange'><b>non-penicillin binding domain </b><scene name='36/365380/4dki_cartoon/17'>(NPB) </scene></font> and a <font color='dodgerblue'><b>transpeptidase <scene name='36/365380/4dki_cartoon/18'>(TP)</scene> binding domain </b></font>. The NPB domain of PBP2a is anchored in the cell membrane, while the TP domain resides in the periplasm with its active site facing the inner surface of the cell wall. The active site contains <scene name='36/365380/Ser403/15'> a serine residue at position 403 (Ser403) which catalyzes the cross-linking of the peptidoglycan rows with pentaglycine cross-links.