Sandbox 128: Difference between revisions

← Older edit

Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

Wayne Decatur, Student, Allison Granberry

@@ Line 28: / Line 28: @@
 ==='''Structure of PBP2a, a B-Lactam Resistant Transpeptidase'''===
-Isolates of methicillin-resistant S. aureus (MRSA) are resistant to almost all currently available B-lactams 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: <font color='orangered'><b>a non-penicillin binding domain </b><scene name='37/372728/Npb_domain/1'>(NPB)</scene></font> and a <font color='dodgerblue'><b>transpeptidase<scene name='37/372728/Tp_domain/1'>TP</scene>-binding domain. The NBP domain of PBP2a is anchored in the cell membrane, while the TP domain residues in the periplasm with its active site facing the inner surface of the cell wall. The active site contains <scene name='37/372724/Serine403label/2'> a serine residue at position 403 (Ser403)</scene>, which catalyzes the cross-linking of the peptidoglycan rows with pentaglycine cross-links.
+Isolates of methicillin-resistant S. aureus (MRSA) are resistant to almost all currently available B-lactams 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: <font color='orangered'><b>a non-penicillin binding domain </b><scene name='37/372728/Npb_domain/1'>(NPB)</scene></font> and a <font color='dodgerblue'>'''transpeptidase'''<scene name='37/372728/Tp_domain/1'>TP</scene>'''-binding domain'''</font>. The NBP domain of PBP2a is anchored in the cell membrane, while the TP domain residues in the periplasm with its active site facing the inner surface of the cell wall. The active site contains <scene name='37/372724/Serine403label/2'> a serine residue at position 403 (Ser403)</scene>, which catalyzes the cross-linking of the peptidoglycan rows with pentaglycine cross-links.
 ==='''B-Lactams that Inhibit PBP2a'''===
-MRSA becomes resistant to almost all B-Lactams by acquiring an alternative TP, PBP2a, that is neither bound nor inhibited by B-Lactams. Recently, two cephlosporins- <scene name='37/372728/Ceftobiprole/3'>ceftobiprole</scene> and ceftaroline- that have anti-MRSA activity have been developed. Ceftobiprole is able to inhibit PBP2a because additional chemical groups at the <scene name='37/372728/R2_group/8'>R2</scene> position of ceftobiprole are able to interact with additional amino acid residues in PBP2a; specifically
+MRSA becomes resistant to almost all B-Lactams by acquiring an alternative TP, PBP2a, that is neither bound nor inhibited by B-Lactams. Recently, two cephlosporins- <scene name='36/365380/Ceftobiprole/28'>ceftobiprole</scene> and ceftaroline- that have anti-MRSA activity have been developed. Ceftobiprole is able to inhibit PBP2a because additional chemical groups at the <scene name='36/365380/Ceftobiprole/29'>R2</scene> position of ceftobiprole are able to interact with additional amino acid residues in PBP2a; specifically <scene name='37/372728/Tyr446_met641_interaction/4'>Tyr446 and Met641, and increase the association of ceftobiprole with PBP2a</scene>. As such, ceftobiprole is (shown as colors of the atom types [[CPK]]) is able to more efficiently react with Ser403 and therefore inhibit the activity of PBP2a.
-<scene name='37/372728/Tyr446_met641_interaction/4'>Tyr446 and Met641, and increase the association of ceftobiprole with PBP2a</scene>.
-As such, ceftobiprole is (shown as colors of the atom types [[CPK]]) is able to more efficiently react with Ser403 and therefore inhibit the activity of PBP2a.
@@ Line 45: / Line 43: @@
 Allosteric site serves as a binding site for the substrate <scene name='36/365380/3zfz_1/25'>peptidoglycan</scene>. When the substrate binds to the <scene name='36/365380/3zfz_1/21'>allosteric site</scene> (Tyr105, Asn146, Asp295, Tyr297), a conformational change occurs at the active site, opening it and allowing catalytic action to occur.
-The medicine, <scene name='36/365380/3zfz_1/24'>ceftaroline</scene>, mimics the substrate at the allosteric site opening the active site, allowing <scene name='36/365380/3zfz_1/22'>ceftaroline</scene> to <scene name='36/365380/3zfz_1/23'>enter and bind noncovalently</scene>.
+The medicine, <scene name='37/372728/Ceftaroline/2'>ceftaroline</scene>, mimics the substrate at the <scene name='37/372728/3zfz_allosteric_site/2'>allosteric site</scene> opening the active site, allowing <scene name='36/365380/3zfz_1/22'>ceftaroline</scene> to <scene name='36/365380/3zfz_1/23'>enter and bind noncovalently</scene>.