Sandbox Reserved 468: Difference between revisions

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'''Hemopexin-like domain'''

The <scene name='Sandbox_Reserved_468/Linker_region/1'>Hemopexin-like domain</scene> starts with Cys259 and forms a complete circle by joining to Cys447 using a disulfide bond that connects and gives this domain the characteristic four-bladed β-propeller structure. Each blade starts near the periphery, in which the Asp residues (Asp266, Asp359 and Asp408) coordinate the central calcium ion through their carbonyl oxygen atom. Glu310 provides the fourth coordination thus completing the acidic patch at the entrance of the central, solvent-accessible channel. The side-chains of these residues form salt bridges to the neighbouring β-strands holding the entrance of the central channel together. Three water molecules are found trapped in the center of this channel but these molecules are not involved in this process. Two of the water molecules are at positions corresponding to the sodium and chloride ion in the proMMP-1 structure. The water molecule corresponding to the sodium ion is at hydrogen-bonding distances to the carbonyl oxygen atom of Ile268, Ala312, Ala361 and Val410.

~~'''Overall Structural Characteristics'''~~

After the initial loop, the sequences follows to the first and longest β-sheet (sI). A second loop precedes large "amphipathic α-helix" (hA) that longitudinally spans protein site. The β-strands sII and sIII follows separated by the respective loops, loop 4 behing commonly designated as "short loop" briging sII to sIII. Following the sIII strand the sequence meets the 'S-shaped double loop' that is of primary importance for the peptide structure and catalytic activity as it extends to the cleft side "bulge", continuing to the only antiparallel β-strand sIV, which is prime importance for binding peptidic substrates or inhibitors by forming main chain Hydrogen bond. Following sIV, loop Gln186-Gly192 and β-strand sV are responsible for contributing with many ligands to the several metal ions present in the protein. A large open loop follows sV which has proven importance in substrate specificity within the MMPs family.

A specific region (183)RWTNNFREY(191) as been identified as a critical segment of matrix metalloproteinase 1 for the expression of collagenolytic activity. On C-terminal part of the CAT Domain the hB α-helix, known as the "active-site helix" encompasses part of the "zinc-binding consensus sequence" HEXXHXXGXXH that is characteristic of the Metzincin superfamily. The α-helix hB finishes abruptly at Gly225 where the last loop of the domain starts. This last loop contains the "specificity loop" which is the shortest in the MMPs family. The Catalytic Domain ends at Gly261 with α-helix hC.

== Mechanism of Action ==

Sandbox Reserved 468: Difference between revisions

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@@ Line 25: / Line 25: @@
 '''Hemopexin-like domain'''
 The <scene name='Sandbox_Reserved_468/Linker_region/1'>Hemopexin-like domain</scene> starts with Cys259 and forms a complete circle by joining to Cys447 using a disulfide bond that connects and gives this domain the characteristic four-bladed β-propeller structure. Each blade starts near the periphery, in which the Asp residues (Asp266, Asp359 and Asp408) coordinate the central calcium ion through their carbonyl oxygen atom. Glu310 provides the fourth coordination thus completing the acidic patch at the entrance of the central, solvent-accessible channel. The side-chains of these residues form salt bridges to the neighbouring β-strands holding the entrance of the central channel together. Three water molecules are found trapped in the center of this channel but these molecules are not involved in this process. Two of the water molecules are at positions corresponding to the sodium and chloride ion in the proMMP-1 structure. The water molecule corresponding to the sodium ion is at hydrogen-bonding distances to the carbonyl oxygen atom of Ile268, Ala312, Ala361 and Val410.
-'''Overall Structural Characteristics'''
-After the initial loop, the sequences follows to the first and longest β-sheet (sI). A second loop precedes large "amphipathic α-helix" (hA) that longitudinally spans protein site. The β-strands sII and sIII follows separated by the respective loops, loop 4 behing commonly designated as "short loop" briging sII to sIII. Following the sIII strand the sequence meets the 'S-shaped double loop' that is of primary importance for the peptide structure and catalytic activity as it extends to the cleft side "bulge", continuing to the only antiparallel β-strand sIV, which is prime importance for binding peptidic substrates or inhibitors by forming main chain Hydrogen bond. Following sIV, loop Gln186-Gly192 and β-strand sV are responsible for contributing with many ligands to the several metal ions present in the protein. A large open loop follows sV which has proven importance in substrate specificity within the MMPs family.
-A specific region (183)RWTNNFREY(191) as been identified as a critical segment of matrix metalloproteinase 1 for the expression of collagenolytic activity. On C-terminal part of the CAT Domain the hB α-helix, known as the "active-site helix" encompasses part of the "zinc-binding consensus sequence" HEXXHXXGXXH that is characteristic of the Metzincin superfamily. The α-helix hB finishes abruptly at Gly225 where the last loop of the domain starts. This last loop contains the "specificity loop" which is the shortest in the MMPs family. The Catalytic Domain ends at Gly261 with α-helix hC.
 == Mechanism of Action ==