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From Proteopedia
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The acylenzyme allows the medium to reach the carbonyle group. As a result, a water molecule can attack the group, causing the cleavage of the tetrahedral structure. | The acylenzyme allows the medium to reach the carbonyle group. As a result, a water molecule can attack the group, causing the cleavage of the tetrahedral structure. | ||
== Structure== | == Structure== | ||
| - | <StructureSection load='3ita' size='340' side='right' caption=' | + | <StructureSection load='3ita' size='340' side='right' caption='PBP6, [[Resolution|resolution]] 1.80Å' scene='80/802673/Default/1'> |
The PBP6 is composed of 4 monomers which are almost identical to each other. The differences are found in some loops and in the amino acids of the active site. | The PBP6 is composed of 4 monomers which are almost identical to each other. The differences are found in some loops and in the amino acids of the active site. | ||
| - | === | + | ===Active site=== |
The amino acids that compose the <scene name='80/802673/Active_site_1/1'>active site</scene> are: Ser40 and Lys43, which organised in a catalytic diad through a hydrogen bond, alongside with Ser106, Asp 108, Lys 209 and Thr 210. | The amino acids that compose the <scene name='80/802673/Active_site_1/1'>active site</scene> are: Ser40 and Lys43, which organised in a catalytic diad through a hydrogen bond, alongside with Ser106, Asp 108, Lys 209 and Thr 210. | ||
The oxygen from Ser40 binds to the carbon from the peptide bond between the two D-alanines, which causes the formation of the acylenzyme complex after the terminal D-alanine leaves. | The oxygen from Ser40 binds to the carbon from the peptide bond between the two D-alanines, which causes the formation of the acylenzyme complex after the terminal D-alanine leaves. | ||
Lys43 deprotonates a catalytic water molecule which then binds to the carbon from the acylenzyme complex in order to regenerate the enzyme and free the peptide which has been shortened by one amino acid. | Lys43 deprotonates a catalytic water molecule which then binds to the carbon from the acylenzyme complex in order to regenerate the enzyme and free the peptide which has been shortened by one amino acid. | ||
| - | Other amino acids allow the selective fixation of the ligand to the enzyme. The residues 79 to 83, 212 to 218 and 242 to 248 are responsible for this. | + | ====Binding site=== |
| + | Other amino acids allow the selective fixation of the ligand to the enzyme. The residues 79 to 83, 212 to 218 and 242 to 248 are responsible for this. These residues undergo a conformation change during substrate fixation. | ||
An example of this is the oxyanion hole, which is a hole in the enzyme structure created by the backbone nitrogens. These nitrogens stabilise the carbonyl oxygen from the D-Ala-D-Ala peptide bond. | An example of this is the oxyanion hole, which is a hole in the enzyme structure created by the backbone nitrogens. These nitrogens stabilise the carbonyl oxygen from the D-Ala-D-Ala peptide bond. | ||
The Ser106, Thr210, Thr212 and Arg244 residues stabilise the C-terminal of the peptide through hydrogen bonds and water molecules (see structure [[3itb]]. | The Ser106, Thr210, Thr212 and Arg244 residues stabilise the C-terminal of the peptide through hydrogen bonds and water molecules (see structure [[3itb]]. | ||
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Penicillin-binding protein 6 from Escherichia coli
The Penicillin-binding protein 6 (PBP6) from Escherichia coli is a DD-carboxypeptidase which plays an important role in the creation of the bacterial cell wall. It belongs to the group of PBP of low molecular mass. Its structure was determined by Chen et al.[1]. These results allow for the study of the functionning of the active site of PBP6 and of the role of pentapeptidic imitation by ampicillin. [2]
Contents |
Function
As a DD-carboxypeptidase, the function of PBP6 is to participate in the transpeptidation which occurs during the biosynthesis of peptidoglycan. More specifically, it cleaves the peptide bond between the two terminal D-alanines of the pentapeptidic muramyl peptides of sequence L-Ala-D-Glu-m-A2pm-D-Ala-D-Ala. This then allows transpeptidases to create peptidoglycan cross-links which stabilise the cell wall. The cleavage reaction takes place in two step. Firstly, the PBP6 binds to carbonyl group in the peptide bond between the two terminal D-alanines of the N-acetylmuramic acid. This forms a high-energy tetrahedric intermediate called the acylenzyme. 3ita shows the acylenzyme complex of PBP6 with ampicillin. The acylenzyme allows the medium to reach the carbonyle group. As a result, a water molecule can attack the group, causing the cleavage of the tetrahedral structure.
Structure
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Relevance
The resolution of this structure played an important role in understanding the method of action of beta-lactam antibiotics[3].
References
- ↑ Chen Y, Zhang W, Shi Q, Hesek D, Lee M, Mobashery S, Shoichet BK. Crystal structures of penicillin-binding protein 6 from Escherichia coli. J Am Chem Soc. 2009 Oct 14;131(40):14345-54. PMID:19807181 doi:10.1021/ja903773f
- ↑ Mattei PJ, Neves D, Dessen A. Bridging cell wall biosynthesis and bacterial morphogenesis. Curr Opin Struct Biol. 2010 Dec;20(6):749-55. doi: 10.1016/j.sbi.2010.09.014., Epub 2010 Oct 26. PMID:21030247 doi:http://dx.doi.org/10.1016/j.sbi.2010.09.014
- ↑ Llarrull LI, Testero SA, Fisher JF, Mobashery S. The future of the beta-lactams. Curr Opin Microbiol. 2010 Oct;13(5):551-7. doi: 10.1016/j.mib.2010.09.008. Epub, 2010 Sep 29. PMID:20888287 doi:http://dx.doi.org/10.1016/j.mib.2010.09.008
