Sandbox Reserved 200: Difference between revisions
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=Introduction= | =Introduction= | ||
[[Image:2D_RNase_A.png|200px|left|thumb|RNase A minor dimer,[[1A2W]]]] | [[Image:2D_RNase_A.png|200px|left|thumb|RNase A minor dimer,[[1A2W]]]] | ||
Bovine pancreatic ribonuclease A [http://en.wikipedia.org/wiki/Ribonuclease_A (RNase A)] is an enzyme that catalyzes the hydrolysis of RNA through [http://www.proteopedia.org/wiki/index.php/Sandbox_Reserved_193 acid-base catalysis]. RNase A has the capability to structurally form dimers, trimers, and other oligomers based on the structure of the [http://www.proteopedia.org/wiki/index.php/Sandbox_Reserved_192 Structure of RNase A monomer]. The oligomers are formed by 3D domain swapping, which can occur once or twice per monomeric unit <ref name="liul">PMID:11224563</ref >. The 3D domain swapping has no impact on the formation of active sites. These same active sites, which are composed of His 12, Lys 41, and His 119, can be found in the monomer, dimer, and trimer <ref name="liul"/>. The oligomers of RNase A also show medical relevance when looking at antitumor drugs as well as the possible cause of Alzheimer's. | Bovine pancreatic ribonuclease A [http://en.wikipedia.org/wiki/Ribonuclease_A (RNase A)] is an enzyme that catalyzes the hydrolysis of RNA through [http://www.proteopedia.org/wiki/index.php/Sandbox_Reserved_193 acid-base catalysis]. RNase A has the capability to structurally form dimers, trimers, and other oligomers based on the structure of the [http://www.proteopedia.org/wiki/index.php/Sandbox_Reserved_192 Structure of RNase A monomer]. Unlike the monomers, these oligomers are capable of catalyzing the hydrolysis of double stranded RNA (dsRNA).<ref name="antitumor"/> The oligomers are formed by 3D domain swapping, which can occur once or twice per monomeric unit <ref name="liul">PMID:11224563</ref >. The 3D domain swapping has no impact on the formation of active sites. These same active sites, which are composed of His 12, Lys 41, and His 119, can be found in the monomer, dimer, and trimer <ref name="liul"/>. The oligomers of RNase A also show medical relevance when looking at antitumor drugs as well as the possible cause of Alzheimer's. | ||
=Dimers= | =Dimers= | ||
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IntroductionIntroduction
Bovine pancreatic ribonuclease A (RNase A) is an enzyme that catalyzes the hydrolysis of RNA through acid-base catalysis. RNase A has the capability to structurally form dimers, trimers, and other oligomers based on the structure of the Structure of RNase A monomer. Unlike the monomers, these oligomers are capable of catalyzing the hydrolysis of double stranded RNA (dsRNA).[1] The oligomers are formed by 3D domain swapping, which can occur once or twice per monomeric unit [2]. The 3D domain swapping has no impact on the formation of active sites. These same active sites, which are composed of His 12, Lys 41, and His 119, can be found in the monomer, dimer, and trimer [2]. The oligomers of RNase A also show medical relevance when looking at antitumor drugs as well as the possible cause of Alzheimer's.
DimersDimers
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Ribonuclease A has both a major and which are very similar to one another. Though they are similar, they are formed by different types of 3D domain swapping. 3D domain swapping occurs when identical domains are interchanged. The is formed by 3D domain swapping the β-strand of the C-terminus.[3] The minor dimer, on the other hand, is formed by 3D domain swapping its α-helix of the N-terminus [3]. Domain swapping is extremely specific and can only occur at the or the .
The two domains of the dimer are linked via the hinge loop.[2]. In the major dimer, the hinge loop is composed of residues 112-115. In the minor dimer, the hinge loop is composed of residues 16-22.[2] The most important component of the hinge loops is Ala19. is the reason that the hinge loops are so flexible . This flexibility allows the dimers to adopt different orientations, for example the major and minor structures.[3]
TrimersTrimers
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Medical RelevanceMedical Relevance
Alzheimer’s disease is a terminal disease that slowly degenerates the brain. One of the possible causes of Alzheimer’s is amyloid deposits throughout the brain. Though RNasa A oligomers are not the amyloid deposits that cause Alzheimer’s the folding of these oligomers gives clues towards the formation of amyloid deposits responsible for Alzheimer’s.
The 3D domain swapping has many similarities with the formation of amyloid fibers. Both are highly specific reactions coming from only one type of monomer and these reactions can form linear aggregates. [4] These aggregates of proteins are formed by hydrogen bonding at the hinge loops which form an antiparalell β-pleated sheet. [4] This most commonly happens with the major dimer. Liu suggests that all proteins are capable of forming aggregates by domain swapping as long as they are in high concentration and partially destabilized. [4] As 3D domain swapping becomes more understood, it will offer insight to the amyloid formation in Alzheimer’s patients.
The RNase A 3D swapped oligomers show significant biological activity including allostery, antitumor, and immunorepression activity. This same activity has not observed in the monomer and the non-3D domain swapped dimers .[3] This could be due to the fact that the monomer has a cystolic RNase A inhibitor that is unable to inhibit the active sites of the oligomers. [4]
Literature CitedLiterature Cited
- ↑ Cite error: Invalid
<ref>tag; no text was provided for refs namedantitumor - ↑ 2.0 2.1 2.2 2.3 Liu Y, Gotte G, Libonati M, Eisenberg D. A domain-swapped RNase A dimer with implications for amyloid formation. Nat Struct Biol. 2001 Mar;8(3):211-4. PMID:11224563 doi:10.1038/84941
- ↑ 3.0 3.1 3.2 3.3 Clemo FA. Urinary enzyme evaluation of nephrotoxicity in the dog. Toxicol Pathol. 1998 Jan-Feb;26(1):29-32. PMID:9502384
- ↑ 4.0 4.1 4.2 4.3 Liu Y, Gotte G, Libonati M, Eisenberg D. Structures of the two 3D domain-swapped RNase A trimers. Protein Sci. 2002 Feb;11(2):371-80. PMID:11790847