Sandbox Reserved 468: Difference between revisions
From Proteopedia
Jump to navigationJump to search
No edit summary |
|||
| Line 16: | Line 16: | ||
== Structure == | == Structure == | ||
The structure of human MMP-1 was determined | The structure of human MMP-1 was determined to have two monomeric structures (chains A and B). However, it is believed that this dimer is not physiologically relevant, as it was found that human MMP-1 is a monomer in solution. The structure of MMP-1, just like the other members of matrix metalloproteinases family, is formed by three different domains. The structure consists of a <scene name='Sandbox_Reserved_468/Catalytic_domain/3'>Catalytic Domain</scene>, a variable Linker Region and the <scene name='Sandbox_Reserved_468/Linker_region/1'>Hemopexin-like domain</scene>. The catalytic domain of one monomer contacts the hemopexin-like domain of the other monomer. These structures were determined by using X-ray crystallography and NMR [2][3]. | ||
Here is the basic structure of a MMP in three different forms. | Here is the basic structure of a MMP in three different forms. | ||
| Line 23: | Line 23: | ||
'''Catalytic Domain''' | '''Catalytic Domain''' | ||
The Catalytic Domains of all MMPs share very similar characteristics, having | The Catalytic Domains of all MMPs share very similar characteristics, having the same general shape and a diameter of ~40Å. The <scene name='Sandbox_Reserved_468/Catalytic_domain/3'>Catalytic Domain</scene> of MMP-1 is composed of five highly twisted β-strands, three α-helix and a total of eight loops, enclosing a total of five metal ions, three Ca2+ and two Zn2+, one of which with catalytic role [2]. The Catalytic Domain (CAT) of MMP-1 starts with the F100 as the first amino-acid of the N-terminal loop of the CAT domain. This is different from the first published x-ray structure of the CAT domain which showed the truncated form of this domain, where the first 7 amino-acids are not present [6]. | ||
Taken from a publication of the crystal structure. | Taken from a publication of the crystal structure. | ||
| Line 30: | Line 30: | ||
'''Linker region''' | '''Linker region''' | ||
In MMPs the catalytic domain is followed by a stretch of 15–65 amino acid residues referred to as the linker or the hinge region. The length of this region varies between MMPs and does not have a well-determined structure. This region is typically rich in proline residues. Interestingly, the replacement of those with alanine drastically reduced the collagenolytic activity of certain MMPs, which may indicate that the presence of the correct linker structure is important for collagenolysis [4]. | In MMPs, the catalytic domain is followed by a stretch of 15–65 amino acid residues referred to as the linker or the hinge region. The length of this region varies between MMPs and does not have a well-determined structure. This region is typically rich in proline residues. Interestingly, the replacement of those with alanine drastically reduced the collagenolytic activity of certain MMPs, which may indicate that the presence of the correct linker structure is important for collagenolysis [4]. | ||
Taken from a publication of the crystal structure. | Taken from a publication of the crystal structure. | ||
| Line 41: | Line 41: | ||
== Mechanism of Action == | == Mechanism of Action == | ||
There is not a generally accepted mechanism of action for this enzyme but there are three possible catalytic mechanisms published. Note that all of these mechanisms somehow involve the zinc ion, which is found in the catalytic domain and believed to play an important role in catalysis. | There is not a generally accepted mechanism of action for this enzyme but there are three possible catalytic mechanisms published. Note that all of these mechanisms somehow involve the zinc ion, which is found in the catalytic domain and believed to play an important role in catalysis. Here is the <scene name='Sandbox_Reserved_468/Active_site/1'>Active Site</scene>. | ||
Taken from a publication of the crystal structure. | Taken from a publication of the crystal structure. | ||
