User:Emily Vago/Sandbox 1 - Revision history

Emily Vago at 03:28, 4 May 2020

2020-05-04T03:28:20Z

←Older revision		Revision as of 03:28, 4 May 2020
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	Understanding the basic “sandwich” motif and crystal structure is key to understanding the important conformational changes that act around the active site. The active site of NDM is located on loop L3, which stretches and deforms in the unbound form; however, there is an expanded β-sheet interaction in the presence of ligand binding<ref name="five"/>. This creates a “zippering effect,” which pulls the L3 loop away from the NDM-1 zinc center, at an increasing distance. In response to this, the side chain M67 faces away from this center, instead, forming a hydrophobic reaction with an R1 ampicillin group<ref name="five"/>. On the other hand, L65 travels toward the center<ref name="five"/>. The result is an R1 phenyl group, comprised of L65, M67, and W93 residues, stabilized by hydrophobic interactions<ref name="five"/>. This results in a more flexible structure, which may potentially impact its likeliness to react with β-lactam antibiotics.		Understanding the basic “sandwich” motif and crystal structure is key to understanding the important conformational changes that act around the active site. The active site of NDM is located on loop L3, which stretches and deforms in the unbound form; however, there is an expanded β-sheet interaction in the presence of ligand binding<ref name="five"/>. This creates a “zippering effect,” which pulls the L3 loop away from the NDM-1 zinc center, at an increasing distance. In response to this, the side chain M67 faces away from this center, instead, forming a hydrophobic reaction with an R1 ampicillin group<ref name="five"/>. On the other hand, L65 travels toward the center<ref name="five"/>. The result is an R1 phenyl group, comprised of L65, M67, and W93 residues, stabilized by hydrophobic interactions<ref name="five"/>. This results in a more flexible structure, which may potentially impact its likeliness to react with β-lactam antibiotics.

-	After ligand-binding interactions, the N220 component of nitrogen moves closer to the zinc center, allowing for interaction with the lactam carbonyl group<ref name="five"/>. Furthermore, the interaction with N220 and zinc-1 creates .an oxyanion hole<ref name="five"/>. The L3 and L10 loops allow for the flexibility of various binding-substrates, as well as with differing biochemical structures.	+	After ligand-binding interactions, the N220 component of nitrogen moves closer to the zinc center, allowing for interaction with the lactam carbonyl group<ref name="five"/>. Furthermore, the interaction with N220 and zinc-1 creates an oxyanion hole<ref name="five"/>. The L3 and L10 loops allow for the flexibility of various binding-substrates, as well as with differing biochemical structures.

	== Protein expression ==		== Protein expression ==

Emily Vago at 03:21, 4 May 2020

2020-05-04T03:21:06Z

←Older revision		Revision as of 03:21, 4 May 2020
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	== Active Site ==		== Active Site ==

-	NDM-1 contains two active sites. The first consists of one water molecule attached to <scene name='84/843929/First_active_site_for_ndm-1/1'>histidine residues 120, 122, and 189</scene><ref name="two"/>. The second active site has three different types of residues: <scene name='84/843929/Second_active_site_for_ndm-1/1'>Asp124, Cys208 and His250</scene~~><ref name="two"/~~>, also containing water molecules<ref name="two"/>.	+	NDM-1 contains two active sites. The first consists of one water molecule attached to <scene name='84/843929/First_active_site_for_ndm-1/1'>histidine residues 120, 122, and 189</scene><ref name="two"/>. The second active site has three different types of residues: <scene name='84/843929/Second_active_site_for_ndm-1/1'>Asp124, Cys208 and His250</scene>, also containing water molecules<ref name="two"/>.

	Understanding the basic “sandwich” motif and crystal structure is key to understanding the important conformational changes that act around the active site. The active site of NDM is located on loop L3, which stretches and deforms in the unbound form; however, there is an expanded β-sheet interaction in the presence of ligand binding<ref name="five"/>. This creates a “zippering effect,” which pulls the L3 loop away from the NDM-1 zinc center, at an increasing distance. In response to this, the side chain M67 faces away from this center, instead, forming a hydrophobic reaction with an R1 ampicillin group<ref name="five"/>. On the other hand, L65 travels toward the center<ref name="five"/>. The result is an R1 phenyl group, comprised of L65, M67, and W93 residues, stabilized by hydrophobic interactions<ref name="five"/>. This results in a more flexible structure, which may potentially impact its likeliness to react with β-lactam antibiotics.		Understanding the basic “sandwich” motif and crystal structure is key to understanding the important conformational changes that act around the active site. The active site of NDM is located on loop L3, which stretches and deforms in the unbound form; however, there is an expanded β-sheet interaction in the presence of ligand binding<ref name="five"/>. This creates a “zippering effect,” which pulls the L3 loop away from the NDM-1 zinc center, at an increasing distance. In response to this, the side chain M67 faces away from this center, instead, forming a hydrophobic reaction with an R1 ampicillin group<ref name="five"/>. On the other hand, L65 travels toward the center<ref name="five"/>. The result is an R1 phenyl group, comprised of L65, M67, and W93 residues, stabilized by hydrophobic interactions<ref name="five"/>. This results in a more flexible structure, which may potentially impact its likeliness to react with β-lactam antibiotics.

Emily Vago at 03:19, 4 May 2020

2020-05-04T03:19:07Z

←Older revision		Revision as of 03:19, 4 May 2020
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	== Structure ==		== Structure ==

-	NDM-1 can be viewed as a hybridized structure, containing distinctive structural elements, as well as enzymes under the same classification system as the B class. NDM-1, a single chain polypeptide, is illustrated by an <scene name='84/843929/~~Secondary_structure_3~~/3'>α-β/β-α ~~“sandwich” motif~~</scene>, which is characteristic of the MBL class<ref name="five"/>. Furthermore, NDM-1 contains an additional β-strand augmentation located at the N terminus; this is accompanied by a β-turn motif<ref name="five">https://doi.org/10.1002/pro.697</ref>. This differentiates the structure from enzymes VIM-2 and IMP-1, other enzymes of the MBL class.	+	NDM-1 can be viewed as a hybridized structure, containing distinctive structural elements, as well as enzymes under the same classification system as the B class. NDM-1, a single chain polypeptide, is illustrated by an <scene name='84/843929/Secondary_structure_4/1'>α-β/β-α</scene> “sandwich” motif, which is characteristic of the MBL class<ref name="five"/>. Furthermore, NDM-1 contains an additional β-strand augmentation located at the N terminus; this is accompanied by a β-turn motif<ref name="five">https://doi.org/10.1002/pro.697</ref>. This differentiates the structure from enzymes VIM-2 and IMP-1, other enzymes of the MBL class.

	'''Crystal structure'''		'''Crystal structure'''

Emily Vago at 03:15, 4 May 2020

2020-05-04T03:15:28Z

←Older revision		Revision as of 03:15, 4 May 2020
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	X-ray structures show that NDM-1 displays three different states: metal free, singly metalated, and doubly metalated. This observation can potentially provide more clues about the binding mechanism of NDM-1, providing noteworthy steps in catalysis, involving the recognition of the ligand sites <ref name="six">https://doi.org/10.1371/journal.pone.0024621</ref>. In response, this would most likely increase the activation center for nucleophilic attack<ref name="six"/>.		X-ray structures show that NDM-1 displays three different states: metal free, singly metalated, and doubly metalated. This observation can potentially provide more clues about the binding mechanism of NDM-1, providing noteworthy steps in catalysis, involving the recognition of the ligand sites <ref name="six">https://doi.org/10.1371/journal.pone.0024621</ref>. In response, this would most likely increase the activation center for nucleophilic attack<ref name="six"/>.
-

	== Conclusion ==		== Conclusion ==

Emily Vago at 03:15, 4 May 2020

2020-05-04T03:15:06Z

←Older revision		Revision as of 03:15, 4 May 2020
Line 35:		Line 35:
	== Protein expression ==		== Protein expression ==

-	Research indicates there is an expression of a Type II lipidation signal peptide, on the N terminus<ref name="five"/>. Studies show that there is a cleavage site between the C26 and M27 ~~residues5~~.	+	Research indicates there is an expression of a Type II lipidation signal peptide, on the N terminus<ref name="five"/>. Studies show that there is a cleavage site between the C26 and M27 residues<ref name="five"/>.

	== Research applications ==		== Research applications ==
Line 48:		Line 48:
	Although β-lactamase, as well as class B MBL, has been widely studied, New Delhi metallo-β-lactamase 1 is still considered a recent evolutionary development. Although ''K. pneumoniae'' is not severely prevalent right now, it is a key example of a bacterial pathogen that has the capability of becoming resistant to β-lactam antibiotics. Analyzing the structure gives scientists further insight as to future topics for study and research. This involves both previous knowledge about broad-spectrum antibiotics and its reaction to bacterial enzymes, such as β-lactamase.		Although β-lactamase, as well as class B MBL, has been widely studied, New Delhi metallo-β-lactamase 1 is still considered a recent evolutionary development. Although ''K. pneumoniae'' is not severely prevalent right now, it is a key example of a bacterial pathogen that has the capability of becoming resistant to β-lactam antibiotics. Analyzing the structure gives scientists further insight as to future topics for study and research. This involves both previous knowledge about broad-spectrum antibiotics and its reaction to bacterial enzymes, such as β-lactamase.

-	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 ==
	<references/>		<references/>

Emily Vago at 03:13, 4 May 2020

2020-05-04T03:13:32Z

←Older revision		Revision as of 03:13, 4 May 2020
Line 19:		Line 19:
	== Structure ==		== Structure ==

-	NDM-1 can be viewed as a hybridized structure, containing distinctive structural elements, as well as enzymes under the same classification system as the B class. NDM-1, a single chain polypeptide, is illustrated by an <scene name='84/843929/~~Secondary_structure_4~~/1'>α-β/β-α</scene> ~~“sandwich” motif~~, which is characteristic of the MBL class<ref name="five"/>. Furthermore, NDM-1 contains an additional β-strand augmentation located at the N terminus; this is accompanied by a β-turn motif<ref name="five">https://doi.org/10.1002/pro.697</ref>. This differentiates the structure from enzymes VIM-2 and IMP-1, other enzymes of the MBL class.	+	NDM-1 can be viewed as a hybridized structure, containing distinctive structural elements, as well as enzymes under the same classification system as the B class. NDM-1, a single chain polypeptide, is illustrated by an <scene name='84/843929/Secondary_structure_3/3'>α-β/β-α “sandwich” motif</scene>, which is characteristic of the MBL class<ref name="five"/>. Furthermore, NDM-1 contains an additional β-strand augmentation located at the N terminus; this is accompanied by a β-turn motif<ref name="five">https://doi.org/10.1002/pro.697</ref>. This differentiates the structure from enzymes VIM-2 and IMP-1, other enzymes of the MBL class.

	'''Crystal structure'''		'''Crystal structure'''
Line 35:		Line 35:
	== Protein expression ==		== Protein expression ==

-	Research indicates there is an expression of a Type II lipidation signal peptide, on the N terminus<ref name="five"/>. Studies show that there is a cleavage site between the C26 and M27 ~~residues<ref name="five"/>~~.	+	Research indicates there is an expression of a Type II lipidation signal peptide, on the N terminus<ref name="five"/>. Studies show that there is a cleavage site between the C26 and M27 residues5.

	== Research applications ==		== Research applications ==
Line 42:		Line 42:

	X-ray structures show that NDM-1 displays three different states: metal free, singly metalated, and doubly metalated. This observation can potentially provide more clues about the binding mechanism of NDM-1, providing noteworthy steps in catalysis, involving the recognition of the ligand sites <ref name="six">https://doi.org/10.1371/journal.pone.0024621</ref>. In response, this would most likely increase the activation center for nucleophilic attack<ref name="six"/>.		X-ray structures show that NDM-1 displays three different states: metal free, singly metalated, and doubly metalated. This observation can potentially provide more clues about the binding mechanism of NDM-1, providing noteworthy steps in catalysis, involving the recognition of the ligand sites <ref name="six">https://doi.org/10.1371/journal.pone.0024621</ref>. In response, this would most likely increase the activation center for nucleophilic attack<ref name="six"/>.
		+

	== Conclusion ==		== Conclusion ==

	Although β-lactamase, as well as class B MBL, has been widely studied, New Delhi metallo-β-lactamase 1 is still considered a recent evolutionary development. Although ''K. pneumoniae'' is not severely prevalent right now, it is a key example of a bacterial pathogen that has the capability of becoming resistant to β-lactam antibiotics. Analyzing the structure gives scientists further insight as to future topics for study and research. This involves both previous knowledge about broad-spectrum antibiotics and its reaction to bacterial enzymes, such as β-lactamase.		Although β-lactamase, as well as class B MBL, has been widely studied, New Delhi metallo-β-lactamase 1 is still considered a recent evolutionary development. Although ''K. pneumoniae'' is not severely prevalent right now, it is a key example of a bacterial pathogen that has the capability of becoming resistant to β-lactam antibiotics. Analyzing the structure gives scientists further insight as to future topics for study and research. This involves both previous knowledge about broad-spectrum antibiotics and its reaction to bacterial enzymes, such as β-lactamase.
		+
		+	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/>

Emily Vago at 03:12, 4 May 2020

2020-05-04T03:12:51Z

←Older revision		Revision as of 03:12, 4 May 2020
Line 42:		Line 42:

	X-ray structures show that NDM-1 displays three different states: metal free, singly metalated, and doubly metalated. This observation can potentially provide more clues about the binding mechanism of NDM-1, providing noteworthy steps in catalysis, involving the recognition of the ligand sites <ref name="six">https://doi.org/10.1371/journal.pone.0024621</ref>. In response, this would most likely increase the activation center for nucleophilic attack<ref name="six"/>.		X-ray structures show that NDM-1 displays three different states: metal free, singly metalated, and doubly metalated. This observation can potentially provide more clues about the binding mechanism of NDM-1, providing noteworthy steps in catalysis, involving the recognition of the ligand sites <ref name="six">https://doi.org/10.1371/journal.pone.0024621</ref>. In response, this would most likely increase the activation center for nucleophilic attack<ref name="six"/>.
-

	== Conclusion ==		== Conclusion ==

	Although β-lactamase, as well as class B MBL, has been widely studied, New Delhi metallo-β-lactamase 1 is still considered a recent evolutionary development. Although ''K. pneumoniae'' is not severely prevalent right now, it is a key example of a bacterial pathogen that has the capability of becoming resistant to β-lactam antibiotics. Analyzing the structure gives scientists further insight as to future topics for study and research. This involves both previous knowledge about broad-spectrum antibiotics and its reaction to bacterial enzymes, such as β-lactamase.		Although β-lactamase, as well as class B MBL, has been widely studied, New Delhi metallo-β-lactamase 1 is still considered a recent evolutionary development. Although ''K. pneumoniae'' is not severely prevalent right now, it is a key example of a bacterial pathogen that has the capability of becoming resistant to β-lactam antibiotics. Analyzing the structure gives scientists further insight as to future topics for study and research. This involves both previous knowledge about broad-spectrum antibiotics and its reaction to bacterial enzymes, such as β-lactamase.

Emily Vago at 03:12, 4 May 2020

2020-05-04T03:12:16Z

←Older revision		Revision as of 03:12, 4 May 2020
Line 47:		Line 47:

	Although β-lactamase, as well as class B MBL, has been widely studied, New Delhi metallo-β-lactamase 1 is still considered a recent evolutionary development. Although ''K. pneumoniae'' is not severely prevalent right now, it is a key example of a bacterial pathogen that has the capability of becoming resistant to β-lactam antibiotics. Analyzing the structure gives scientists further insight as to future topics for study and research. This involves both previous knowledge about broad-spectrum antibiotics and its reaction to bacterial enzymes, such as β-lactamase.		Although β-lactamase, as well as class B MBL, has been widely studied, New Delhi metallo-β-lactamase 1 is still considered a recent evolutionary development. Although ''K. pneumoniae'' is not severely prevalent right now, it is a key example of a bacterial pathogen that has the capability of becoming resistant to β-lactam antibiotics. Analyzing the structure gives scientists further insight as to future topics for study and research. This involves both previous knowledge about broad-spectrum antibiotics and its reaction to bacterial enzymes, such as β-lactamase.
-
-	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/>

Emily Vago at 03:06, 4 May 2020

2020-05-04T03:06:03Z

←Older revision		Revision as of 03:06, 4 May 2020
Line 35:		Line 35:
	== Protein expression ==		== Protein expression ==

-	Research indicates there is an expression of a Type II lipidation signal peptide, on the N terminus<ref name="five"/>. Studies show that there is a cleavage site between the C26 and M27 ~~residues5~~.	+	Research indicates there is an expression of a Type II lipidation signal peptide, on the N terminus<ref name="five"/>. Studies show that there is a cleavage site between the C26 and M27 residues<ref name="five"/>.

	== Research applications ==		== Research applications ==

Emily Vago at 03:05, 4 May 2020

2020-05-04T03:05:14Z

←Older revision		Revision as of 03:05, 4 May 2020
Line 19:		Line 19:
	== Structure ==		== Structure ==

-	NDM-1 can be viewed as a hybridized structure, containing distinctive structural elements, as well as enzymes under the same classification system as the B class. NDM-1, a single chain polypeptide, is illustrated by an <scene name='84/843929/~~Secondary_structure_3~~/3'>α-β/β-α ~~“sandwich” motif~~</scene>, which is characteristic of the MBL class<ref name="five"/>. Furthermore, NDM-1 contains an additional β-strand augmentation located at the N terminus; this is accompanied by a β-turn motif<ref name="five">https://doi.org/10.1002/pro.697</ref>. This differentiates the structure from enzymes VIM-2 and IMP-1, other enzymes of the MBL class.	+	NDM-1 can be viewed as a hybridized structure, containing distinctive structural elements, as well as enzymes under the same classification system as the B class. NDM-1, a single chain polypeptide, is illustrated by an <scene name='84/843929/Secondary_structure_4/1'>α-β/β-α</scene> “sandwich” motif, which is characteristic of the MBL class<ref name="five"/>. Furthermore, NDM-1 contains an additional β-strand augmentation located at the N terminus; this is accompanied by a β-turn motif<ref name="five">https://doi.org/10.1002/pro.697</ref>. This differentiates the structure from enzymes VIM-2 and IMP-1, other enzymes of the MBL class.

	'''Crystal structure'''		'''Crystal structure'''