HIV-1 p24

GWB-F48F6D

BDI499Host Animal: Mouse

Recognizes HIV-1 p24 (native antigen)

Lot specific (OD280nm E0. 1% = 1. 4)Preservatives: NaN3

This product contains sodium azide which has been classified as Xn (Harmful) in European Directive 67/548/EEC in the concentration range of 0. 1â ??1. 0%. When disposing of this reagent through lead or copper plumbing flush with copious volumes of water to prevent azide build-up in drains. MAb to HIV-1 p24. Monoclonal Antibody to Human Immunodeficiency Virus Type 1 (HIV-1) p24 specific

Matrix protein p17 has two main functions: in infected cell it targets Gag and Gag-pol polyproteins to the plasma membrane via a multipartite membrane-binding signal that includes its myristoylated N-terminus. The second function is to plays a role in nuclear localization of the viral genome at the very start of cell infection. Matrix protein is the part of the pre-integration complex. It binds in the cytoplasm the human BAF protein which prevent autointegration of the viral genome and might be included in virions at the ration of zero to 3 BAF dimer per virion. The myristoylation signal and the NLS thus exert conflicting influences its subcellular localization. The key regulation of these motifs might be phosphorylation of a portion of MA molecules on the C-terminal tyrosine at the time of virus maturation by virion-associated cellular tyrosine kinase. Implicated in the release from host cell mediated by Vpu.

Nucleocapsid protein p7 encapsulates and protects viral dimeric unspliced (genomic) RNA. Binds these RNAs through its zinc fingers. Facilitates rearangement of nucleic acid secondary structure during retrotranscription of genomic RNA. This capability is referred to as nucleic acid chaperone activity.

Reverse transcriptase/ribonuclease H (RT) is a multifunctional enzyme that converts the viral RNA genome into dsDNA in the cytoplasm shortly after virus entry into the cell. This enzyme displays a DNA polymerase activity that can copy either DNA or RNA templates and a ribonuclease H (RNase H) activity that cleaves the RNA strand of RNA-DNA heteroduplexes in a partially processive 3\' to 5\' endonucleasic mode. Conversion of viral genomic RNA into dsDNA requires many steps. A tRNA(3)-Lys binds to the primer-binding site (PBS) situated at the 5\' -end of the viral RNA. RT uses the 3\' end of the tRNA primer to perform a short round of RNA-dependent minus-strand DNA synthesis. The reading proceeds through the U5 region and ends after the repeated (R) region which is present at both ends of viral RNA. The portion of the RNA-DNA heteroduplex is digested by the RNase H resulting in a ssDNA product attached to the tRNA primer. This ssDNA/tRNA hybridizes with the identical R region situated at the 3\' end of viral RNA. This template exchange known as minus-strand DNA strong stop transfer can be either intra- or intermolecular. RT uses the 3\' end of this newly synthesized short ssDNA to perform the RNA-dependent minus-strand DNA synthesis of the whole template. RNase H digests the RNA template except for two polypurine tracts (PPTs) situated at the 5\' -end and near the center of the genome. It is not clear if both polymerase and RNase H activities are simultaneous. RNase H probably can proceed both in a polymerase-dependent (RNA cut into small fragments by the same RT performing DNA synthesis) and a polymerase-independent mode (cleavage of remaining RNA fragments by free RTs). Secondly RT performs DNA-directed plus-strand DNA synthesis using the PPTs that have not been removed by RNase H as primers. PPTs and tRNA primers are then removed by RNase H. The 3\' and 5\' ssDNA PBS regions hybridize to form a circular dsDNA intermediate. Strand displacement synthesis by RT to the PBS and PPT ends produces a blunt ended linear dsDNA copy of the viral genome that includes long terminal repeats (LTRs) at both ends.

Specific for a P1 residue that is hydrophobic and P1\' variable but often Pro.

Deoxynucleoside triphosphate + DNA(n) = diphosphate + DNA(n+1). Cofactor: Binds 2 magnesium ions for reverse transcriptase polymerase activity (By similarity). Cofactor: Binds 2 magnesium ions for ribonuclease H (RNase H) activity. Substrate-binding is a precondition for magnesium binding (By similarity). Cofactor: Magnesium ions for integrase activity. Binds at least 1 maybe 2 magnesium ions (By similarity). Enzyme Regulation: The viral protease is inhibited by many synthetic protease inhibitors (PIs) such as amprenavir atazanavir indinavir loprinavir nelfinavir ritonavir and saquinavir. RT can be inhibited either by nucleoside RT inhibitors (NRTIs) or by non nucleoside RT inhibitors (NNRTIs). NRTIs act as chain terminators whereas NNRTIs inhibit DNA polymerization by binding a small hydrophobic pocket near the RT active site and inducing an allosteric change in this region. Classical NRTIs are abacavir adefovir (PMEA) didanosine (ddI) lamivudine (3TC) stavudine (d4T) tenofovir (PMPA) zalcitabine (ddC) and zidovudine (AZT). Classical NNRTIs are atevirdine (BHAP U-87201E) delavirdine efavirenz (DMP-266) emivirine (I-EBU) and nevirapine (BI-RG-587). The tritherapies used as a basic effective treatment of AIDS associate two NRTIs and one NNRTI. Use of protease inhibitors in tritherapy regimens permit more ambitious therapeutic strategies. Subunit: Pre-integration complex interacts with human HMGA1. Matrix protein p17 is a trimer. Interacts with gp120 and human BAF. Capsid is a homodimer. Interacts with human PPIA/CYPA. The protease is a homodimer whose active site consists of two apposed aspartic acid residues. The reverse transcriptase is a heterodimer of p66 RT and p51 RT (RT p66/p51). Heterodimerization of RT is essential for DNA polymerase activity. Despite the sequence identities p66 RT and p51 RT have distinct folding. Integrase is a homodimer and possibly can form homotetramer. Integrase interacts with human SMARCB1/INI1 and human PSIP1/LEDGF isoform 1. Subcellular Location: Matrix protein p17: Virion (Potential). Nucleus (By similarity). Cytoplasm (By similarity). Cell membrane; Lipid-anchor (Potential). Note=Following virus entry the nuclear localization signal (NLS) of the matrix protein participates with Vpr to the nuclear localization of the viral genome. During virus production the nuclear export activity of the matrix protein counteracts the NLS to maintain the Gag and Gag-Pol polyproteins in the cytoplasm thereby directing unspliced RNA to the plasma membrane (By similarity). Subcellular Location: Capsid protein p24: Virion (Potential). Subcellular Location: Nucleocapsid protein p7: Virion (Potential). Subcellular Location: Reverse transcriptase/ribonuclease H: Virion (Potential). Subcellular Location: Integrase: Virion (Potential). Nucleus (Potential). Cytoplasm (Potential). Note=Nuclear at initial phase cytoplasmic at assembly (Potential). Domain: The reverse transcriptase/ribonuclease H (RT) is structured in five subdomains: finger palm thumb connection and RNase H. Within the palm subdomain the \' primer grip\' region is thought to be involved in the positioning of the primer terminus for accomodating the incoming nucleotide. The RNase H domain stabilizes the association of RT with primer-template (By similarity). Domain: The tryptophan repeat motif is involved in RT p66/p51 dimerization. Domain: Integrase core domain contains the D-x(n)-D-x(35)-E motif named for the phylogenetically conserved glutamic acid and aspartic acid residues and the invariant 35 amino acid spacing between the second and third acidic residues. Each acidic residue of the D D(35)E motif is independently essential for the 3\' -processing and strand transfer activities of purified integrase protein. Ptm: Specific enzymatic cleavages by the viral protease yield mature proteins. The protease is released by autocatalytic cleavage. The polyprotein is cleaved during and after budding this process is termed maturation. Proteolytic cleavage of p66 RT removes the RNase H domain to yield the p51 RT subunit. Nucleocapsid protein p7 might be further cleaved after virus entry. Ptm: Capsid protein p24 is phosphorylated. Ptm: Matrix protein p17 is tyrosine phosphorylated presumably in the virion by a host kinase. This modification targets the matrix protein to the nucleus. Miscellaneous: Capsid protein p24 is able to bind macaque TRIM5-alpha or owl monkey TRIMCyp preventing reverse transcription of the viral genome and succesfull infection of macaque or owl monkey by HIV-1. Miscellaneous: The reverse transcriptase is an error-prone enzyme that lacks a proof-reading function. High mutations rate is a direct consequence of this characteristic. RT also displays frequent template switching leading to high recombination rate. Recombination mostly occurs between homologous regions of the two copackaged RNA genomes. If these two RNA molecules derive from different viral strains reverse transcription will give rise to highly recombinated proviral DNAs. Miscellaneous: HIV-1 lineages are divided in three main groups M (for Major) O (for Outlier) and N (for New or Non-M Non-O). The vast majority of strains found worldwide belong to the group M. Group O seems to be endemic to and largely confined to Cameroon and neighboring countries in West Central Africa where these viruses represent a small minority of HIV-1 strains. The group N is represented by a limited number of isolates from Cameroonian persons. The group M is further subdivided in 9 clades or subtypes (A to D F to H J and K). Miscellaneous: Resistance to inhibitors associated with mutations are observed both in viral protease and in reverse transcriptase. Most of the time single mutations confer only a modest reduction in drug susceptibility. Combination of several mutations is usually required to develop a high-level drug resistance. These mutations are predominantly found in clade B viruses and not in other genotypes. They are listed in this entry which is a representative of clade B. Similarity: Contains 2 CCHC-type zinc fingers. Similarity: Contains 1 integrase catalytic domain. Similarity: Contains 1 integrase-type DNA-binding domain. Similarity: Contains 1 integrase-type zinc finger. Similarity: Contains 1 peptidase A2 domain [view classification]. Similarity: Contains 1 reverse transcriptase domain. Similarity: Contains 1 RNase H domain.