Sandbox GGC7

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== Structure E28A mutant of the HIV-1==
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==Iduronate 2-sulfatase==
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<scene name='75/752270/Mutation_of_the_hiv-1_capsid_p/1'>Mutant of the HIV-1 Capsid p</scene>
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<StructureSection load='5FQL' size='340' side='right' caption='Iduronate 2-sulfatase protein' scene=''>
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<StructureSection load='5CSR' size='340' side='right' caption='Triose phosphate isomerase' scene=''>
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Iduronate 2-sulfatase (IDS), also referred to as Alpha-L-iduronate sulfate sulfatase or Idursulfase, is a lysosomal enzyme involved in the degradation pathway of dermatan sulfate and heparan sulfate.[1]
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<scene name='75/752270/Spacefill_mutant_hiv_-1/3'>Spacefill mutant HIV-1</scene>
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<scene name='75/752270/Ca_hexamer_interfaces/3'>Ca Hexamer interfaces</scene>
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== Function ==
== Function ==
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The function of the HIV-1 capsid protein is to encapsidate and protect the viral RNA genome. It contains important sites on its surface that allow the virion to be attach to the host cell. The CA protein a key has an important role in early and late stages of the HIV virus replication cycle.
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Iduronate 2-sulfatase is located in the lysosome.[1] It is involved in the lysosomal degradation pathway of dermatan sulfate and heparan sulfate.[1] IDS hydrolyzes the 2-sulfate groups of the L-iduronate 2-sulfate units of dermatan sulfate, heparan sulfate and heparin.[1] Dermatan sulfate and heparan sulfate are complex glycosaminoglycans, which are essentially large sugar molecules.[2] They play important roles in cell adhesion, growth, proliferation and repair, and their degradation and recycling in the lysosome are essential for cellular maintenance.[2] IDS is expressed in the tissues of the liver, kidney, lung, and placenta.[1]
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The HIV capsid is built from a single protein, known as capsid protein (CA). The protein folds to form two domains the N-terminal and C-terminal connected by a small flexible linker.
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== Disease ==
== Disease ==
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HIV infection (Human Immunodeficiency virus) The virus attacks the cells in the body that help to fight infection, causing weakness in the immune system and making the person’s liable for any infection or disease. HIV can be spread by unprotected intercourse, blood, breast milk, body fluids.
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Mutations in Iduronate 2-sulfatase on the Xq28 chromosome can lead to Mucopolysaccharidosis 2 (MPS2), more commonly known as Hunter syndrome.[1] MPS2 is an X-linked lysosomal storage disease.[1] Due to the loss of IDS activity, the disease is characterized by the intracellular accumulation of the glycosaminoglycans heparan sulfate and dermatan sulfate, which are then excreted in urine.[1] Scientists have identified over 500 mutations on the Xq28 chromosome that include rearrangements, insertions/deletions, splicing defects and nonsense point mutations.[2] It is rare to find adults with severe Hunter syndrome as the average life expectancy for those with MPS2 is 15 years of age.[1] Most children diagnosed with MPS2 have somatic abnormalities including skeletal deformities, hepatosplenomegaly, and progressive cardiopulmonary deterioration.[1] Neurological damage is also prevalent beginning with what seems to be a developmental delay and hyperactivity, but progresses to mental retardation and dementia.[1] Death from MPS2 is typically due to obstructive airway disease or cardiac failure.[1] A treatment for patients with mild Hunter syndrome is enzyme replacement therapy, which involves the recombinant human IDS.[2]
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[[Image:Signs-and-symptoms-of-hunter-syndrome.jpg]]
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== Relevance ==
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The studies of the HIV capsid in this case Mutagenesis and structural experiments have revealed that capsid core stability affects uncoating and initiation of reverse transcription in host cells. The studies have led to efforts in developing antivirals targeting the capsid protein and its assembly.
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== Structural highlights ==
== Structural highlights ==
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Mutant of the HIV-1 Capsid p.The structure on the scene is the E28A mutant of the HIV-1 Capsid protein. The green balls are the Cl ion and the purple are Iodide ions. The structure was loaded and the color was changed to model the 6 chains connected together by a flexible linker to form the hexamers which encloses the viral RNA.
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<scene name='75/752270/Ide_mutations/1'>Scene 1: Location of mutations</scene>
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Scene two structural highlights
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Spacefill mutant HIV-1, the image displays the 6 proteins connected forming the hexamer and the N terminal domain pocket in the center this is important because is not a crucial binding site and displays low backbone deformation and mobility and shows less hydrogen binding which makes it a good target area to create an antiviral inhibitor.
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Scene three structural highlights
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Ca Hexamer interfaces, this is the image of the backbone of the inner surface of the CA, that is formed by two neighboring CA N- terminal domain interface pocked and is capped at one end by the R18 sidechains and by interaction of the E28-K30 on the other end. The two side chains are slightly separated that it is difficult to form hydrogen bonding. This led to explore the identification of sensitive interactions of the CA interfaces using biochemical analysis that lead to develop new antivirals targeting the stability of CA assemblies.
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<scene name='75/752270/Ide_atp_binding-active_sites/1'>Scene 2: ATP binding active sites</scene>
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<scene name='75/752270/Ide_n_and_c_terminals/1'>Scene 3: N and C terminals</scene>
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<scene name='75/752270/Active_site_on_chain_a/1'>Scene 4: Active sites</scene>
</StructureSection>
</StructureSection>
== References ==
== References ==
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http://proteopedia.org/wiki/index.php/5w4p
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1. UniProt ConsortiumEuropean Bioinformatics InstituteProtein Information ResourceSIB Swiss Institute of Bioinformatics. Iduronate 2-sulfatase https://www.uniprot.org/uniprot/P22304#pathology_and_biotech (accessed Apr 28, 2021).
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https://www.rcsb.org/structure/5W4P
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2. Demydchuk M, Hill CH, Zhou A, Bunkóczi G, Stein PE, Marchesan D, Deane JE, Read RJ. Insights into Hunter syndrome from the structure of iduronate-2-sulfatase. Nat Commun. 2017 Jun 8;8:15786. doi: 10.1038/ncomms15786. PMID: 28593992; PMCID: PMC5472762.
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<references/>
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Current revision

Iduronate 2-sulfatase

Iduronate 2-sulfatase protein

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References

1. UniProt ConsortiumEuropean Bioinformatics InstituteProtein Information ResourceSIB Swiss Institute of Bioinformatics. Iduronate 2-sulfatase https://www.uniprot.org/uniprot/P22304#pathology_and_biotech (accessed Apr 28, 2021). 2. Demydchuk M, Hill CH, Zhou A, Bunkóczi G, Stein PE, Marchesan D, Deane JE, Read RJ. Insights into Hunter syndrome from the structure of iduronate-2-sulfatase. Nat Commun. 2017 Jun 8;8:15786. doi: 10.1038/ncomms15786. PMID: 28593992; PMCID: PMC5472762.

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