Sandbox Reserved 646: Difference between revisions

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== '''Structure''' ==

'''~~Isomers'~~''

'''Isoforms & Topology''

Arginase is unique because of all the enzymes found in the urea cycle this enzyme has different isoforms. In the human body there are two isozymes with similar structural properties and differing immunological properties. Common among the differing isozymes is the requirement of two divalent cation cofactors for activity. Manganese2+ is the most common cofactor for activity but cobalt, nickel and iron have been reported to be suitable cofactors as well. The two required manganese II ions are located in two separate subunits and are separated by approximately 3.36-3.57 Å and bridged by oxygen and a solvent derived hydroxide <ref>Ash, David Structure and Function of Arginases [http://www.ncbi.nlm.nih.gov/pubmed/15465781]</ref> Many varying isoforms of arginase have produced different structural models based on the particular isoform and organism of origin. The most well studied arginase enzyme, arginase I isolated from rat liver, is a trimeric enzyme and each subunit is ordered in an alpha-beta-alpha structure. Each fold contains an eight-stranded, parallel β-sheet surrounded by alpha helices, with an approximate size 35kDa <ref>Ash, David Structure and Function of Arginases [http://www.ncbi.nlm.nih.gov/pubmed/15465781]</ref>. Fully active enzymes contain a binuclear metal cofactor center in a 15Å cleft that serves as the active site. One cofactor is held in place by terminal ligands His 101 and Asp 128, and bridged by Asp 124, Asp 132 and hydroxide ion <ref>Ash, David Structure and Function of Arginases [http://www.ncbi.nlm.nih.gov/pubmed/15465781]</ref>. The other cofactor held by terminal ligand residues His 101 and Asp 234 with bridging ligands Asp 232 and hydroxide ion <ref>Ash, David Structure and Function of Arginases [http://www.ncbi.nlm.nih.gov/pubmed/15465781]</ref>.

Although arginase is present in different isoforms, there is a high level of conservation among the amino acids. For example, human type I and IIarginases share a 58% sequence identity (Ash). Overall, there are 20 amino acids that are highly conserved over the varying isoforms. Most of these conserved residues are key structural residues. Included in these conserved structural residues is gly 23, which begins the first α-helix of arginase(Perozich). In addition to highly conserved nucleotides, there exist a few key invariant nucleotides as well. Among the most notable are Val 120, Ile 121, Val 233 and Ile 264 which are attributed to the packing of the hydrophobic interior of the protein (Perozich).

~~'''Topology'''~~

== '''Medical Application''' ==

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@@ Line 16: / Line 16: @@
 == '''Structure''' ==
-'''Isomers'''
+'''Isoforms & Topology''
+Arginase is unique because of all the enzymes found in the urea cycle this enzyme has different isoforms.  In the human body there are two isozymes with similar structural properties and differing immunological properties. Common among the differing isozymes is the requirement of two divalent cation cofactors for activity. Manganese2+ is the most common cofactor for activity but cobalt, nickel and iron have been reported to be suitable cofactors as well. The two required manganese II ions are located in two separate subunits and are separated by approximately 3.36-3.57 Å and bridged by oxygen and a solvent derived hydroxide <ref>Ash, David Structure and Function of Arginases [http://www.ncbi.nlm.nih.gov/pubmed/15465781]</ref>  Many varying isoforms of arginase have produced different structural models based on the particular isoform and organism of origin. The most well studied arginase enzyme, arginase I isolated from rat liver, is a trimeric enzyme and each subunit is ordered in an alpha-beta-alpha structure. Each fold contains an eight-stranded, parallel β-sheet surrounded by alpha helices, with an approximate size 35kDa <ref>Ash, David Structure and Function of Arginases [http://www.ncbi.nlm.nih.gov/pubmed/15465781]</ref>. Fully active enzymes contain a binuclear metal cofactor center in a 15Å cleft that serves as the active site. One cofactor is held in place by terminal ligands His 101 and Asp 128, and bridged by Asp 124, Asp 132 and hydroxide ion <ref>Ash, David Structure and Function of Arginases [http://www.ncbi.nlm.nih.gov/pubmed/15465781]</ref>. The other cofactor held by terminal ligand residues His 101 and Asp 234 with bridging ligands Asp 232 and  hydroxide ion <ref>Ash, David Structure and Function of Arginases [http://www.ncbi.nlm.nih.gov/pubmed/15465781]</ref>.
+Although arginase is present in different isoforms, there is a high level of conservation among the amino acids. For example, human type I and IIarginases share a 58% sequence identity (Ash).  Overall, there are 20 amino acids that are highly conserved over the varying isoforms. Most of these conserved residues are key structural residues. Included in these conserved structural residues is gly 23, which begins the first α-helix of arginase(Perozich).  In addition to highly conserved nucleotides, there exist a few key invariant nucleotides as well. Among the most notable are Val 120, Ile 121, Val 233 and Ile 264 which are attributed to the packing of the hydrophobic interior of the protein (Perozich).
-'''Topology'''
 == '''Medical Application''' ==