Sandbox Reserved 478: Difference between revisions
No edit summary |
No edit summary |
||
| (One intermediate revision by the same user not shown) | |||
| Line 16: | Line 16: | ||
===Hemopexin-like Domain=== | ===Hemopexin-like Domain=== | ||
The <scene name='Sandbox_Reserved_478/Hemopexin/1'>Hemopexin-like Domain</scene> consists of about 210 amino acids and is composed of four Hemopexin modules (I-IV), each representing a blade of the beta-propeller structure. Each blade starts with either the DAA or DAX motif, in which Asp residues direct the central calcium ion through their carbonyl oxygen atom. <ref>J Li, P Brick, MC O'Hare, T Skarzynski, LF Lloyd, VA Curry, IM Clark, HF Bigg, BL Hazleman, TE Cawston, DM Blow, Structure of full-length porcine synovial collagenase reveals a C-terminal domain containing a calcium-linked, four-bladed β-propeller, Structure, Volume 3, Issue 6, June 1995, Pages 541-549</ref> <ref name=" | The <scene name='Sandbox_Reserved_478/Hemopexin/1'>Hemopexin-like Domain</scene> consists of about 210 amino acids and is composed of four Hemopexin modules (I-IV), each representing a blade of the beta-propeller structure. Each blade starts with either the DAA or DAX motif, in which Asp residues direct the central calcium ion through their carbonyl oxygen atom. <ref>J Li, P Brick, MC O'Hare, T Skarzynski, LF Lloyd, VA Curry, IM Clark, HF Bigg, BL Hazleman, TE Cawston, DM Blow, Structure of full-length porcine synovial collagenase reveals a C-terminal domain containing a calcium-linked, four-bladed β-propeller, Structure, Volume 3, Issue 6, June 1995, Pages 541-549</ref> <ref name="lyer" /> Glu310 also provides the fourth coordination thus completing the acidic patch at the entrance of the central, solvent-accessible channel. The side chains of these residues also help to form salt bridges with β-strands and hold the entrance of the central channel inline. | ||
Three molecules of water are held within the center of the central channel and they are not involved in the geometry of the calcium ion at the center of the tunnel. It has been reasoned that the presence of these ions is not related to the stability conditions but rather a consequence of the crystallization methods. | Three molecules of water are held within the center of the central channel and they are not involved in the geometry of the calcium ion at the center of the tunnel. It has been reasoned that the presence of these ions is not related to the stability conditions but rather a consequence of the crystallization methods. | ||
| Line 22: | Line 22: | ||
Several Studies have been conducted on the specific mechanism of MMPs, and many different perspectives of the mechanism have been published. The difference in the proposed mechanisms shows that the research within this area is still undergoing and there is no final verdict as to the mechanism of action. Robert Visse et al, states in a review of Matrix Metalloproteinases, that MMPs can be activated by proteinases or in vitro by chemical agents, such as thiol-modifying agents (4-aminophenylmercuric acetate, HgCl2, and N-ethylmaleimide), oxidized glutathione, SDS, chaotropic agents, and reactive oxygens. <ref name="Visse" /> These agents mostly work to disturb the interaction between the cysteine-zinc of the cysteine switch. Proteolytic activation of MMPs is stepwise with the initial proteolytic attack occuring at an exposed loop region between the first and the second helices of the propeptide, once a portion of the propetide is removed, then the rest of the propeptide is destabilized which allows for the intermolecular processing by partially activated MMP intermediates or other MMPs. The final step in the activation process is therefore conducted by an MMP | Several Studies have been conducted on the specific mechanism of MMPs, and many different perspectives of the mechanism have been published. The difference in the proposed mechanisms shows that the research within this area is still undergoing and there is no final verdict as to the mechanism of action. Robert Visse et al, states in a review of Matrix Metalloproteinases, that MMPs can be activated by proteinases or in vitro by chemical agents, such as thiol-modifying agents (4-aminophenylmercuric acetate, HgCl2, and N-ethylmaleimide), oxidized glutathione, SDS, chaotropic agents, and reactive oxygens. <ref name="Visse" /> These agents mostly work to disturb the interaction between the cysteine-zinc of the cysteine switch. Proteolytic activation of MMPs is stepwise with the initial proteolytic attack occuring at an exposed loop region between the first and the second helices of the propeptide, once a portion of the propetide is removed, then the rest of the propeptide is destabilized which allows for the intermolecular processing by partially activated MMP intermediates or other MMPs. The final step in the activation process is therefore conducted by an MMP | ||
This image is a representation of the mode of activation that is utilized in MMP-1. the image is used to show activation in human colleganase (proMMP-1)[[Image:F3large.jpg]] | This image is a representation of the mode of activation that is utilized in MMP-1. the image is used to show activation in human colleganase (proMMP-1)<ref name="Visse" /> [[Image:F3large.jpg]] | ||
==Medical Implications== | ==Medical Implications== | ||