Sandbox Reserved 429
From Proteopedia
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==Overall Structure== | ==Overall Structure== | ||
| - | Penicillin Binding Proteins have specific structures and designs that promote allow the binding of Penicillin and other antibiotics. One of the enzymes within the PBP family is <scene name='48/483886/D-alanyl-d-alanine_carboxypept/1'>D-alanyl-D-alanine carboxypeptidase/transpeptidase</scene>. This enzyme is responsible for the link between two chains in the peptidoglycan network | + | Penicillin Binding Proteins have specific structures and designs that promote allow the binding of Penicillin and other antibiotics. One of the enzymes within the PBP family is <scene name='48/483886/D-alanyl-d-alanine_carboxypept/1'>D-alanyl-D-alanine carboxypeptidase/transpeptidase</scene>. This enzyme is responsible for the link between two chains in the peptidoglycan network <ref> Goodsell, David. "Penicillin-binding Proteins." Penicillin-binding Proteins. May 2002. Web. 07 Apr. 2016.<ref>. DA-DA peptidase’s structure contains a serine in the active site. Ser 62 is used to bind a peptide strand which would then link to another strand of the network, and this is the site where penicillin binds and inhibits the protein. |
| - | This enzyme is split into two sections, which will be referred to as the North and South regions. The North Region contains both the carboxyl and amino termini, two α-helices, and a nine-stranded antiparallel β-sheet | + | This enzyme is split into two sections, which will be referred to as the North and South regions. The North Region contains both the carboxyl and amino termini, two α-helices, and a nine-stranded antiparallel β-sheet <ref> Kelly, J. A., and A. P. Kuzin. "3PTE." RCSB PDB. Web. 07 Apr. 2016.<ref>. This leads the Northern region of the enzyme to appear symmetrical. Both termini lead are connected to helices and then into β-strands. Inbetween the sets of strands the South region of the peptide is formed and this is strictly made out of helices. In the center of the two regions is where the Ser 62 active site resides, and this is also at the symmetrical center of the protein. The protein essentially forms a cupped hand, with the center of the palm being the active site, the bottom of the palm being a series of 8 or so helices, the knuckles being the β-strands, and the tips of the fingers being the two helices of the North region. |
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Antibiotics resistance is the property of bacteria that have receive relatively low effectiveness by antibiotic. With the overproduction and overusing of antibiotics, more bacteria have low resistance to antibiotic are killed than the bacteria have high resistance. Under the evolutionary pressure, the remaining group of bacteria have relatively high resistance which means that the normal antibiotics have less effectiveness or do not have effectiveness anymore. As penicillin-binding proteins playing an important role at bacteria’s cell synthesis and β-lactams antibiotics inhibiting bacterial division by binding penicillin-binding proteins, antibiotics resistance also emerges to the penicillin-binding proteins and makes penicillin-binding proteins have low affinity for penicillins. | Antibiotics resistance is the property of bacteria that have receive relatively low effectiveness by antibiotic. With the overproduction and overusing of antibiotics, more bacteria have low resistance to antibiotic are killed than the bacteria have high resistance. Under the evolutionary pressure, the remaining group of bacteria have relatively high resistance which means that the normal antibiotics have less effectiveness or do not have effectiveness anymore. As penicillin-binding proteins playing an important role at bacteria’s cell synthesis and β-lactams antibiotics inhibiting bacterial division by binding penicillin-binding proteins, antibiotics resistance also emerges to the penicillin-binding proteins and makes penicillin-binding proteins have low affinity for penicillins. | ||
| - | Normally, the bacteria produce the penicillin binding proteins with low penicillin-affinity<scene name='48/483886/Conserved_residues_of_pbp/2'>low affinity</scene> by transformation, which is a kind of gene modification. Through this way, bacteria could have a relatively higher resistance to β-lactams antibiotics. But staphylococcus is a special case, it strengthens the drug resistance by two ways instead of gene exchange. By the raised dissociation constants for the non-covalent pre-acylation and the dropped penicillin-sensitive microscopic rate constant for acylation, staphylococcus enhance its own drug resistance. | + | Normally, the bacteria produce the penicillin binding proteins with low penicillin-affinity<scene name='48/483886/Conserved_residues_of_pbp/2'>low affinity</scene> by transformation, which is a kind of gene modification. Through this way, bacteria could have a relatively higher resistance to β-lactams antibiotics. But staphylococcus is a special case, it strengthens the drug resistance by two ways instead of gene exchange. By the raised dissociation constants for the non-covalent pre-acylation and the dropped penicillin-sensitive microscopic rate constant for acylation, staphylococcus enhance its own drug resistance.<ref>PMID:15226303<ref> |
And the solution to the penicillin binding proteins drug resistance could be semi-synthetic β-lactams. The mechanism is that semi-synthetic β-lactams have the alternative side chain compared to the normal penicillins and it will make penicillin binding proteins have the higher affinity to it and as a result the increasing drug resistance will be solved.[4] | And the solution to the penicillin binding proteins drug resistance could be semi-synthetic β-lactams. The mechanism is that semi-synthetic β-lactams have the alternative side chain compared to the normal penicillins and it will make penicillin binding proteins have the higher affinity to it and as a result the increasing drug resistance will be solved.[4] | ||
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==References== | ==References== | ||
<references/> | <references/> | ||
| - | 1. Goodsell, David. "Penicillin-binding Proteins." Penicillin-binding Proteins. May 2002. Web. 07 Apr. 2016. | ||
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| - | 2. Kelly, J. A., and A. P. Kuzin. "3PTE." RCSB PDB. Web. 07 Apr. 2016. | ||
3. Cosimo Fuda, Maxim Suvorov, Sergei B. Vakulenko and Shahriar Mobashery. “The Basis for Resistance to β-Lactam Antibiotics by Penicillin-binding Protein 2a of Methicillin-resistant Staphylococcus aureus.” June 28, 2004 | 3. Cosimo Fuda, Maxim Suvorov, Sergei B. Vakulenko and Shahriar Mobashery. “The Basis for Resistance to β-Lactam Antibiotics by Penicillin-binding Protein 2a of Methicillin-resistant Staphylococcus aureus.” June 28, 2004 | ||
4. Ohi N, Aoki B, Shinozaki T, Moro K, Noto T, Nehashi T, Okazaki H and Matsunaga I. “Semisynthetic beta-lactam antibiotics. I. Synthesis and antibacterial activity of new ureidopenicillin derivatives having catechol moieties. “1986 Feb | 4. Ohi N, Aoki B, Shinozaki T, Moro K, Noto T, Nehashi T, Okazaki H and Matsunaga I. “Semisynthetic beta-lactam antibiotics. I. Synthesis and antibacterial activity of new ureidopenicillin derivatives having catechol moieties. “1986 Feb | ||
Revision as of 20:16, 10 April 2016
| This Sandbox is Reserved from January 19, 2016, through August 31, 2016 for use for Proteopedia Team Projects by the class Chemistry 423 Biochemistry for Chemists taught by Lynmarie K Thompson at University of Massachusetts Amherst, USA. This reservation includes Sandbox Reserved 425 through Sandbox Reserved 439. |
Penicillin binding protein/lactivicin (inhibitor) (2jch)[1]
by Tyler Carpenter, Samuel Pierce, Hyunjoon Choi, Anton El Khoury and Tiankai Zhang
Student Projects for UMass Chemistry 423 Spring 2016
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