Sandbox GGC7: Difference between revisions

Line 7:

== Structure ==

The structure of IDE is a <scene name='75/752270/Ide_homodimer/2'>homodimer</scene> with N-terminal domains, which forms the catalytic site and the C-terminal domains that facilitates the substrate binding <ref>DOI 10.1074/jbc.M900068200</ref>. The N-terminal domains are connected to the C-terminal domains via a 28-residue loop that forms a chamber that is shaped like a triangular prism.

Domain 1 houses the <scene name='75/752270/Ide_monomer/1'>metal binding site</scene> with two histidine's and one glutamine(his 108, his 112 and ~~glu~~ 198), the <scene name='75/752270/Ide_atp_binding-active_sites/1'>active site</scene> of a glutamine (~~Glu~~ 111), ATP binding site (Arg 429) and the Zn2+ ion cofactor. Several residues of domains 1 & 4 create a polar area of the triangular cavity, while residues of domains 2 & 3 create a nonpolar region of the cavity.

Domain 1 houses the <scene name='75/752270/Ide_monomer/1'>metal binding site</scene> with two histidine's and one glutamine(his 108, his 112 and gln 198), the <scene name='75/752270/Ide_atp_binding-active_sites/1'>active site</scene> of a glutamine (Gln 111), ATP binding site (Arg 429) and the Zn2+ ion cofactor. Several residues of domains 1 & 4 create a polar area of the triangular cavity, while residues of domains 2 & 3 create a nonpolar region of the cavity.

There are two conformations for the enzyme, open and closed. In the open conformation, the insulin protein enters the enzyme opening causing a conformational change that allows the enzyme to fully recognize the protein and catalyzes protein degradation.

Line 15:

== Disease ==

The ability of the human metabolism to create and degrade the hormone insulin is an essential process that needs to be turned on or off quickly and if the body cannot process insulin or degrade amyloid beta-proteins properly then the buildup of both of these proteins can cause diabetes or Alzheimer’s to develop. Several mutations of the insulin-degrading enzyme can cause these and other diseases. A mutation of ~~Glu~~ 111, which is the active site, will render the enzyme inactive and a mutation at Pro 286 will slow down the enzymatic activity.

The ability of the human metabolism to create and degrade the hormone insulin is an essential process that needs to be turned on or off quickly and if the body cannot process insulin or degrade amyloid beta-proteins properly then the buildup of both of these proteins can cause diabetes or Alzheimer’s to develop. Several mutations of the insulin-degrading enzyme can cause these and other diseases. A mutation of Gln 111, which is the active site, will render the enzyme inactive and a mutation at Pro 286 will slow down the enzymatic activity.

For insulin, if it is allowed to build up, insulin resistance can occur and contribute to the development of type II diabetes <ref>doi:10.1016/s0002-9440(10)63229-4</ref>. A mutation at Asp 34 will cause Hyperproinsulinemia <ref>doi:10.1210/endo.135.2.8033810</ref><ref>doi:10.1212/01.wnl.0000140292.04932.87</ref>, a disease where the body secretes insulin before it has been fully processed (proinsulin) and so does not function properly. This disease will cause diabetes as a secondary disease. Several different mutations at birth or a young age can contribute to the onset of <scene name='75/752270/Ide_mutations/1'>>neonatal diabetes</scene> or type I diabetes. The locations are: Asp 24, Arg 32, Gly 43, Val 47, Cys 48, Cys 89, Cys 90, Tyr 96 and Cys 108.

Sandbox GGC7: Difference between revisions

Navigation menu

Page actions

Page actions

Personal tools

Navigation

Search

Tools

@@ Line 7: / Line 7: @@
 == Structure ==
 The structure of IDE is a <scene name='75/752270/Ide_homodimer/2'>homodimer</scene> with N-terminal domains, which forms the catalytic site and the C-terminal domains that facilitates the substrate binding <ref>DOI 10.1074/jbc.M900068200</ref>. The N-terminal domains are connected to the C-terminal domains via a 28-residue loop that forms a chamber that is shaped like a triangular prism.
-Domain 1 houses the <scene name='75/752270/Ide_monomer/1'>metal binding site</scene> with two histidine's and one glutamine(his 108, his 112 and glu 198), the <scene name='75/752270/Ide_atp_binding-active_sites/1'>active site</scene> of a glutamine (Glu 111), ATP binding site (Arg 429) and the Zn2+ ion cofactor. Several residues of domains 1 & 4 create a polar area of the triangular cavity, while residues of domains 2 & 3 create a nonpolar region of the cavity.
+Domain 1 houses the <scene name='75/752270/Ide_monomer/1'>metal binding site</scene> with two histidine's and one glutamine(his 108, his 112 and gln 198), the <scene name='75/752270/Ide_atp_binding-active_sites/1'>active site</scene> of a glutamine (Gln 111), ATP binding site (Arg 429) and the Zn2+ ion cofactor. Several residues of domains 1 & 4 create a polar area of the triangular cavity, while residues of domains 2 & 3 create a nonpolar region of the cavity.
 There are two conformations for the enzyme, open and closed.  In the open conformation, the insulin protein enters the enzyme opening causing a conformational change that allows the enzyme to fully recognize the protein and catalyzes protein degradation.
@@ Line 15: / Line 15: @@
 == Disease ==
-The ability of the human metabolism to create and degrade the hormone insulin is an essential process that needs to be turned on or off quickly and if the body cannot process insulin or degrade amyloid beta-proteins properly then the buildup of both of these proteins can cause diabetes or Alzheimer’s to develop.  Several mutations of the insulin-degrading enzyme can cause these and other diseases.  A mutation of Glu 111, which is the active site, will render the enzyme inactive and a mutation at Pro 286 will slow down the enzymatic activity.
+The ability of the human metabolism to create and degrade the hormone insulin is an essential process that needs to be turned on or off quickly and if the body cannot process insulin or degrade amyloid beta-proteins properly then the buildup of both of these proteins can cause diabetes or Alzheimer’s to develop.  Several mutations of the insulin-degrading enzyme can cause these and other diseases.  A mutation of Gln 111, which is the active site, will render the enzyme inactive and a mutation at Pro 286 will slow down the enzymatic activity.
 For insulin, if it is allowed to build up, insulin resistance can occur and contribute to the development of type II diabetes <ref>doi:10.1016/s0002-9440(10)63229-4</ref>. A mutation at Asp 34 will cause Hyperproinsulinemia <ref>doi:10.1210/endo.135.2.8033810</ref><ref>doi:10.1212/01.wnl.0000140292.04932.87</ref>, a disease where the body secretes insulin before it has been fully processed (proinsulin) and so does not function properly.  This disease will cause diabetes as a secondary disease.  Several different mutations at birth or a young age can contribute to the onset of <scene name='75/752270/Ide_mutations/1'>>neonatal diabetes</scene> or type I diabetes. The locations are: Asp 24, Arg 32, Gly 43, Val 47, Cys 48, Cys 89, Cys 90, Tyr 96 and Cys 108.