How B-lactam drugs work - Revision history

Alexander Berchansky at 13:52, 20 March 2024

Alexander Berchansky — Wed, 20 Mar 2024 13:52:35 GMT

←Older revision		Revision as of 13:52, 20 March 2024
Line 15:		Line 15:
	For more information about penicillin binding proteins, please see the Molecule of the Month page for penicillin binding proteins. [https://pdb101.rcsb.org/motm/29] and [[Penicillin-binding protein]].		For more information about penicillin binding proteins, please see the Molecule of the Month page for penicillin binding proteins. [https://pdb101.rcsb.org/motm/29] and [[Penicillin-binding protein]].

-		+	See also [[Beta-lactam antibiotics]]
	</StructureSection>		</StructureSection>
	== References ==		== References ==
	<references/>		<references/>

Michal Harel at 09:34, 12 January 2020

Michal Harel — Sun, 12 Jan 2020 09:34:32 GMT

←Older revision		Revision as of 09:34, 12 January 2020
Line 13:		Line 13:
	How do bacteria become resistant to penicillin and other beta lactam antibiotics? Some bacteria have an enzyme called penicillinase, which inactivates penicillin by cutting the beta lactam ring to form a carboxylic acid and an amine. This prevents the antibiotic from reacting with the serine residue in the transpeptidase, making it inactive. The gene for this enzyme is located on a bacterial plasmid, and can be transferred from one bacteria to another, causing antibacterial resistance to spread.		How do bacteria become resistant to penicillin and other beta lactam antibiotics? Some bacteria have an enzyme called penicillinase, which inactivates penicillin by cutting the beta lactam ring to form a carboxylic acid and an amine. This prevents the antibiotic from reacting with the serine residue in the transpeptidase, making it inactive. The gene for this enzyme is located on a bacterial plasmid, and can be transferred from one bacteria to another, causing antibacterial resistance to spread.

-	For more information about penicillin binding proteins, please see the Molecule of the Month page for penicillin binding proteins. [https://pdb101.rcsb.org/motm/29]	+	For more information about penicillin binding proteins, please see the Molecule of the Month page for penicillin binding proteins. [https://pdb101.rcsb.org/motm/29] and [[Penicillin-binding protein]].

Michal Harel at 09:31, 12 January 2020

Michal Harel — Sun, 12 Jan 2020 09:31:42 GMT

←Older revision		Revision as of 09:31, 12 January 2020
Line 1:		Line 1:
	==How beta-lactam drugs work==		==How beta-lactam drugs work==
-	<StructureSection load='1CEG' size='340' side='right' caption='transpeptidase' scene=''>	+	<StructureSection load='1CEG' size='340' side='right' caption='D-alanyl-D-alanine carboxipeptidase transpeptidase complex with cephalothin (PDB code [[1ceg]])' scene=''>

	Beta-lactam drugs are a classic way of treating bacterial infections. Since bacteria have cell walls and people don't, drugs that target cell wall synthesis should have fewer side effects. Beta-lactam drugs include penicillin, which was discovered by 1928 by Alexander Fleming. He observed that colonies of Penicillium mold growing in his bacterial cultures created zones where bacteria couldn't grow.<ref>PMID:26243971</ref> He then isolated the specific compound that was responsible for this effect, penicillin. The term "beta lactam" refers to the four membered ring structure that is found in this class of antibiotics. [[Image:DalaDala_vs_penicillin.png\|left\|300 px]]		Beta-lactam drugs are a classic way of treating bacterial infections. Since bacteria have cell walls and people don't, drugs that target cell wall synthesis should have fewer side effects. Beta-lactam drugs include penicillin, which was discovered by 1928 by Alexander Fleming. He observed that colonies of Penicillium mold growing in his bacterial cultures created zones where bacteria couldn't grow.<ref>PMID:26243971</ref> He then isolated the specific compound that was responsible for this effect, penicillin. The term "beta lactam" refers to the four membered ring structure that is found in this class of antibiotics. [[Image:DalaDala_vs_penicillin.png\|left\|300 px]]

Ann Taylor at 19:53, 17 April 2019

Ann Taylor — Wed, 17 Apr 2019 19:53:22 GMT

←Older revision		Revision as of 19:53, 17 April 2019
Line 9:		Line 9:


-	The beta lactam antibiotic <scene name='81/814024/B_lactam_in_hole/1'>binds in this groove of the protein</scene>. The groove also contains a <scene name='81/814024/Ser_62/1'>serine residue</scene> that is important for the catalysis of the peptide bond formation. Instead of reacting with the normal peptide substrate, the serine residue has formed a <scene name='81/814024/Ser_62_measurement/1'>covalent bond</scene> with the carbonyl carbon of the beta lactam, as can be seen by its bond length (a C-O bond is 0.14 nm), and the increased distance between the carbonyl carbon and the <scene name='81/814024/C_n_bond_measurement/1'>nitrogen it bonds to in the lactam ring</scene> (a normal C-N bond distance is 0.15 nm; this is almost double that distance). This prevents the normal substrate, the D-ala peptide fragments, from binding to the enzyme, preventing the crosslinking of the bacterial cell wall. Because the antibiotic is attached to the enzyme via a covalent bond, it doesn't come off easily, and the enzyme is essentially "dead".	+	The beta lactam antibiotic <scene name='81/814024/B_lactam_in_hole/1'>binds in this groove of the protein</scene>. The groove also contains a <scene name='81/814024/Ser_62/1'>serine residue</scene> that is important for the catalysis of the peptide bond formation. Instead of reacting with the normal peptide substrate, the serine residue has formed a <scene name='81/814024/Ser_62_measurement/1'>covalent bond</scene> with the carbonyl carbon of the beta lactam, as can be seen by its bond length (a C-O bond is 0.14 nm), and the increased distance between the carbonyl carbon and the <scene name='81/814024/C_n_bond_measurement/1'>nitrogen it bonds to in the lactam ring</scene> (a normal C-N bond distance is 0.15 nm; this is almost double that distance). This prevents the normal substrate, the D-ala peptide fragments, from binding to the enzyme, preventing the crosslinking of the bacterial cell wall. Because the antibiotic is attached to the enzyme via a covalent bond, it doesn't come off easily, and the enzyme is essentially "dead". <ref>PMID:7626623</ref>

	How do bacteria become resistant to penicillin and other beta lactam antibiotics? Some bacteria have an enzyme called penicillinase, which inactivates penicillin by cutting the beta lactam ring to form a carboxylic acid and an amine. This prevents the antibiotic from reacting with the serine residue in the transpeptidase, making it inactive. The gene for this enzyme is located on a bacterial plasmid, and can be transferred from one bacteria to another, causing antibacterial resistance to spread.		How do bacteria become resistant to penicillin and other beta lactam antibiotics? Some bacteria have an enzyme called penicillinase, which inactivates penicillin by cutting the beta lactam ring to form a carboxylic acid and an amine. This prevents the antibiotic from reacting with the serine residue in the transpeptidase, making it inactive. The gene for this enzyme is located on a bacterial plasmid, and can be transferred from one bacteria to another, causing antibacterial resistance to spread.

		+	For more information about penicillin binding proteins, please see the Molecule of the Month page for penicillin binding proteins. [https://pdb101.rcsb.org/motm/29]

Ann Taylor at 19:49, 17 April 2019

Ann Taylor — Wed, 17 Apr 2019 19:49:35 GMT

←Older revision		Revision as of 19:49, 17 April 2019
Line 9:		Line 9:


-	The beta lactam antibiotic <scene name='81/814024/B_lactam_in_hole/1'>binds in this groove of the protein</scene>. The groove also contains a <scene name='81/814024/Ser_62/1'>serine residue</scene> that is important for the catalysis of the peptide bond formation. Instead of reacting with the normal peptide substrate, the serine residue has formed a <scene name='81/814024/Ser_62_measurement/1'>covalent bond</scene> with the carbonyl carbon of the beta lactam, as can be seen by its bond length (a C-O bond is 0.14 nm), and the increased distance between the carbonyl carbon and the <scene name='81/814024/C_n_bond_measurement/1'>nitrogen it bonds to in the lactam ring</scene> (a normal C-N bond distance is 0.15 nm; this is almost double that distance).	+	The beta lactam antibiotic <scene name='81/814024/B_lactam_in_hole/1'>binds in this groove of the protein</scene>. The groove also contains a <scene name='81/814024/Ser_62/1'>serine residue</scene> that is important for the catalysis of the peptide bond formation. Instead of reacting with the normal peptide substrate, the serine residue has formed a <scene name='81/814024/Ser_62_measurement/1'>covalent bond</scene> with the carbonyl carbon of the beta lactam, as can be seen by its bond length (a C-O bond is 0.14 nm), and the increased distance between the carbonyl carbon and the <scene name='81/814024/C_n_bond_measurement/1'>nitrogen it bonds to in the lactam ring</scene> (a normal C-N bond distance is 0.15 nm; this is almost double that distance). This prevents the normal substrate, the D-ala peptide fragments, from binding to the enzyme, preventing the crosslinking of the bacterial cell wall. Because the antibiotic is attached to the enzyme via a covalent bond, it doesn't come off easily, and the enzyme is essentially "dead".
		+
		+	How do bacteria become resistant to penicillin and other beta lactam antibiotics? Some bacteria have an enzyme called penicillinase, which inactivates penicillin by cutting the beta lactam ring to form a carboxylic acid and an amine. This prevents the antibiotic from reacting with the serine residue in the transpeptidase, making it inactive. The gene for this enzyme is located on a bacterial plasmid, and can be transferred from one bacteria to another, causing antibacterial resistance to spread.

Ann Taylor at 19:42, 17 April 2019

Ann Taylor — Wed, 17 Apr 2019 19:42:44 GMT

←Older revision		Revision as of 19:42, 17 April 2019
Line 2:		Line 2:
	<StructureSection load='1CEG' size='340' side='right' caption='transpeptidase' scene=''>		<StructureSection load='1CEG' size='340' side='right' caption='transpeptidase' scene=''>

-	Beta-lactam drugs are a classic way of treating bacterial infections. Since bacteria have cell walls and people don't, drugs that target cell wall synthesis should have fewer side effects. Beta-lactam drugs include penicillin, which was discovered by 1928 by Alexander Fleming. He observed that colonies of Penicillium mold growing in his bacterial cultures created zones where bacteria couldn't grow.<ref>PMID:26243971</ref> He then isolated the specific compound that was responsible for this effect, penicillin. The term "beta lactam" refers to the four membered ring structure that is found in this class of antibiotics.	+	Beta-lactam drugs are a classic way of treating bacterial infections. Since bacteria have cell walls and people don't, drugs that target cell wall synthesis should have fewer side effects. Beta-lactam drugs include penicillin, which was discovered by 1928 by Alexander Fleming. He observed that colonies of Penicillium mold growing in his bacterial cultures created zones where bacteria couldn't grow.<ref>PMID:26243971</ref> He then isolated the specific compound that was responsible for this effect, penicillin. The term "beta lactam" refers to the four membered ring structure that is found in this class of antibiotics. [[Image:DalaDala_vs_penicillin.png\|left\|300 px]]

-	The enzyme that penicillin and other beta-lactam antibiotics target is transpeptidase, which is involved in cell wall synthesis. It creates peptide crosslinks in the cell wall. When transpeptidase is inhibited, the cells burst from osmotic pressure. The transpeptidase <scene name='81/814024/Secondary_structure/1'>secondary structure </scene> consists of an antiparallel beta sheet, with a small alpha helical subdomain on one side and a large alpha helical domain on the other. The surface of the beta sheet creates a groove where the substrate peptides can bind.


-	The beta lactam ~~antibiotic <scene name='81/814024/B_lactam_in_hole/1'>binds~~ in ~~this groove of~~ the ~~protein</scene>~~. ~~The groove also contains a <scene name='81/814024/Ser_62/1'>serine residue</scene> that~~ is ~~important for~~ the ~~catalysis of the peptide bond formation~~. ~~Instead of reacting with the normal peptide substrate, the serine residue has formed a~~ <scene name='81/814024/~~Ser_62_measurement~~/1'>~~covalent bond~~</scene> ~~with the carbonyl carbon~~ of ~~the~~ beta ~~lactam~~, ~~as can be seen by its bond length (~~a ~~C-O bond is 0.14 nm),~~ and the ~~increased distance between~~ the ~~carbonyl carbon and~~ the ~~<scene name='81/814024/C_n_bond_measurement/1'>nitrogen it bonds to in the lactam ring</scene> (a normal C-N bond distance is 0.15 nm; this is almost double that distance)~~.	+	The enzyme that penicillin and other beta-lactam antibiotics target is transpeptidase, which is involved in cell wall synthesis. It creates peptide crosslinks in the cell wall. When transpeptidase is inhibited, the cells burst from osmotic pressure. The transpeptidase <scene name='81/814024/Secondary_structure/1'>secondary structure </scene> consists of an antiparallel beta sheet, with a small alpha helical subdomain on one side and a large alpha helical domain on the other. The surface of the beta sheet creates a groove where the substrate peptides can bind.


		+	The beta lactam antibiotic <scene name='81/814024/B_lactam_in_hole/1'>binds in this groove of the protein</scene>. The groove also contains a <scene name='81/814024/Ser_62/1'>serine residue</scene> that is important for the catalysis of the peptide bond formation. Instead of reacting with the normal peptide substrate, the serine residue has formed a <scene name='81/814024/Ser_62_measurement/1'>covalent bond</scene> with the carbonyl carbon of the beta lactam, as can be seen by its bond length (a C-O bond is 0.14 nm), and the increased distance between the carbonyl carbon and the <scene name='81/814024/C_n_bond_measurement/1'>nitrogen it bonds to in the lactam ring</scene> (a normal C-N bond distance is 0.15 nm; this is almost double that distance).

Ann Taylor at 19:11, 17 April 2019

Ann Taylor — Wed, 17 Apr 2019 19:11:51 GMT

←Older revision		Revision as of 19:11, 17 April 2019
Line 2:		Line 2:
	<StructureSection load='1CEG' size='340' side='right' caption='transpeptidase' scene=''>		<StructureSection load='1CEG' size='340' side='right' caption='transpeptidase' scene=''>

-	Beta-lactam drugs are a classic way of treating bacterial infections. Since bacteria have cell walls and people don't, drugs that target cell wall synthesis should have fewer side effects. Beta-lactam drugs include penicillin, which was discovered by 1928 by Alexander Fleming. He observed that colonies of Penicillium mold growing in his bacterial cultures created zones where bacteria couldn't grow. He then isolated the specific compound that was responsible for this effect, penicillin. The term "beta lactam" refers to the four membered ring structure that is found in this class of antibiotics.	+	Beta-lactam drugs are a classic way of treating bacterial infections. Since bacteria have cell walls and people don't, drugs that target cell wall synthesis should have fewer side effects. Beta-lactam drugs include penicillin, which was discovered by 1928 by Alexander Fleming. He observed that colonies of Penicillium mold growing in his bacterial cultures created zones where bacteria couldn't grow.<ref>PMID:26243971</ref> He then isolated the specific compound that was responsible for this effect, penicillin. The term "beta lactam" refers to the four membered ring structure that is found in this class of antibiotics.
		+
		+	The enzyme that penicillin and other beta-lactam antibiotics target is transpeptidase, which is involved in cell wall synthesis. It creates peptide crosslinks in the cell wall. When transpeptidase is inhibited, the cells burst from osmotic pressure. The transpeptidase <scene name='81/814024/Secondary_structure/1'>secondary structure </scene> consists of an antiparallel beta sheet, with a small alpha helical subdomain on one side and a large alpha helical domain on the other. The surface of the beta sheet creates a groove where the substrate peptides can bind.
		+
		+
		+	The beta lactam antibiotic <scene name='81/814024/B_lactam_in_hole/1'>binds in this groove of the protein</scene>. The groove also contains a <scene name='81/814024/Ser_62/1'>serine residue</scene> that is important for the catalysis of the peptide bond formation. Instead of reacting with the normal peptide substrate, the serine residue has formed a <scene name='81/814024/Ser_62_measurement/1'>covalent bond</scene> with the carbonyl carbon of the beta lactam, as can be seen by its bond length (a C-O bond is 0.14 nm), and the increased distance between the carbonyl carbon and the <scene name='81/814024/C_n_bond_measurement/1'>nitrogen it bonds to in the lactam ring</scene> (a normal C-N bond distance is 0.15 nm; this is almost double that distance).

-	The enzyme that penicillin and other beta-lactam antibiotics target is transpeptidase, which is involved in cell wall synthesis. It creates peptide crosslinks in the cell wall. When transpeptidase is inhibited, the cells burst from osmotic pressure. The beta lactam antibiotic <scene name='81/814024/B_lactam_in_hole/1'>binds in a groove of the protein</scene> where the peptide substrates usually bind. In this groove is a <scene name='81/814024/Ser_62/1'>serine residue</scene> that is important for the catalysis of the peptide bond formation. Instead of reacting with the normal peptide substrate, the serine residue has formed a <scene name='81/814024/Ser_62_measurement/1'>covalent bond</scene> with the carbonyl carbon of the beta lactam, as can be seen by its bond length (a C-O bond is 0.14 nm), and the increased distance between the carbonyl carbon and the <scene name='81/814024/C_n_bond_measurement/1'>nitrogen it bonds to in the lactam ring</scene> (a normal C-N bond distance is 0.15 nm; this is almost double that distance).

-	You may include any references to papers as in: the use of JSmol in Proteopedia <ref>DOI 10.1002/ijch.201300024</ref> or to the article describing Jmol <ref>PMID:21638687</ref> to the rescue.

Ann Taylor at 18:59, 17 April 2019

Ann Taylor — Wed, 17 Apr 2019 18:59:21 GMT

←Older revision		Revision as of 18:59, 17 April 2019
Line 1:		Line 1:
	==How beta-lactam drugs work==		==How beta-lactam drugs work==
-	<StructureSection load='~~3pt3~~' size='340' side='right' caption='transpeptidase' scene=''>	+	<StructureSection load='1CEG' size='340' side='right' caption='transpeptidase' scene=''>

	Beta-lactam drugs are a classic way of treating bacterial infections. Since bacteria have cell walls and people don't, drugs that target cell wall synthesis should have fewer side effects. Beta-lactam drugs include penicillin, which was discovered by 1928 by Alexander Fleming. He observed that colonies of Penicillium mold growing in his bacterial cultures created zones where bacteria couldn't grow. He then isolated the specific compound that was responsible for this effect, penicillin. The term "beta lactam" refers to the four membered ring structure that is found in this class of antibiotics.		Beta-lactam drugs are a classic way of treating bacterial infections. Since bacteria have cell walls and people don't, drugs that target cell wall synthesis should have fewer side effects. Beta-lactam drugs include penicillin, which was discovered by 1928 by Alexander Fleming. He observed that colonies of Penicillium mold growing in his bacterial cultures created zones where bacteria couldn't grow. He then isolated the specific compound that was responsible for this effect, penicillin. The term "beta lactam" refers to the four membered ring structure that is found in this class of antibiotics.

-	The enzyme that penicillin and other beta-lactam antibiotics target is transpeptidase, which is involved in cell wall synthesis. It creates peptide crosslinks in the cell wall. When transpeptidase is inhibited, the cells burst from osmotic pressure.	+	The enzyme that penicillin and other beta-lactam antibiotics target is transpeptidase, which is involved in cell wall synthesis. It creates peptide crosslinks in the cell wall. When transpeptidase is inhibited, the cells burst from osmotic pressure. The beta lactam antibiotic <scene name='81/814024/B_lactam_in_hole/1'>binds in a groove of the protein</scene> where the peptide substrates usually bind. In this groove is a <scene name='81/814024/Ser_62/1'>serine residue</scene> that is important for the catalysis of the peptide bond formation. Instead of reacting with the normal peptide substrate, the serine residue has formed a <scene name='81/814024/Ser_62_measurement/1'>covalent bond</scene> with the carbonyl carbon of the beta lactam, as can be seen by its bond length (a C-O bond is 0.14 nm), and the increased distance between the carbonyl carbon and the <scene name='81/814024/C_n_bond_measurement/1'>nitrogen it bonds to in the lactam ring</scene> (a normal C-N bond distance is 0.15 nm; this is almost double that distance).

	You may include any references to papers as in: the use of JSmol in Proteopedia <ref>DOI 10.1002/ijch.201300024</ref> or to the article describing Jmol <ref>PMID:21638687</ref> to the rescue.		You may include any references to papers as in: the use of JSmol in Proteopedia <ref>DOI 10.1002/ijch.201300024</ref> or to the article describing Jmol <ref>PMID:21638687</ref> to the rescue.

-	== Function ==

-	== Disease ==
-
-	== Relevance ==
-
-	== Structural highlights ==
-
-	This is a sample scene created with SAT to <scene name="/12/3456/Sample/1">color</scene> by Group, and another to make <scene name="/12/3456/Sample/2">a transparent representation</scene> of the protein. You can make your own scenes on SAT starting from scratch or loading and editing one of these sample scenes.

	</StructureSection>		</StructureSection>
	== References ==		== References ==
	<references/>		<references/>

Ann Taylor: New page: ==How beta-lactam drugs work== Beta-lactam drugs are a classic way of treating bacterial infection...

Ann Taylor — Wed, 17 Apr 2019 18:05:12 GMT

New page: ==How beta-lactam drugs work== <StructureSection load='3pt3' size='340' side='right' caption='transpeptidase' scene=''> Beta-lactam drugs are a classic way of treating bacterial infection...

New page

==How beta-lactam drugs work==
<StructureSection load='3pt3' size='340' side='right' caption='transpeptidase' scene=''>

Beta-lactam drugs are a classic way of treating bacterial infections. Since bacteria have cell walls and people don't, drugs that target cell wall synthesis should have fewer side effects. Beta-lactam drugs include penicillin, which was discovered by 1928 by Alexander Fleming. He observed that colonies of Penicillium mold growing in his bacterial cultures created zones where bacteria couldn't grow. He then isolated the specific compound that was responsible for this effect, penicillin. The term "beta lactam" refers to the four membered ring structure that is found in this class of antibiotics.

The enzyme that penicillin and other beta-lactam antibiotics target is transpeptidase, which is involved in cell wall synthesis. It creates peptide crosslinks in the cell wall. When transpeptidase is inhibited, the cells burst from osmotic pressure.

You may include any references to papers as in: the use of JSmol in Proteopedia <ref>DOI 10.1002/ijch.201300024</ref> or to the article describing Jmol <ref>PMID:21638687</ref> to the rescue.

== Function ==

== Disease ==

== Relevance ==

== Structural highlights ==

This is a sample scene created with SAT to <scene name="/12/3456/Sample/1">color</scene> by Group, and another to make <scene name="/12/3456/Sample/2">a transparent representation</scene> of the protein. You can make your own scenes on SAT starting from scratch or loading and editing one of these sample scenes.

</StructureSection>
== References ==
<references/>