2bgr

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<StructureSection load='2bgr' size='340' side='right'caption='[[2bgr]], [[Resolution|resolution]] 2.00&Aring;' scene=''>
<StructureSection load='2bgr' size='340' side='right'caption='[[2bgr]], [[Resolution|resolution]] 2.00&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
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<table><tr><td colspan='2'>[[2bgr]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2BGR OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2BGR FirstGlance]. <br>
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<table><tr><td colspan='2'>[[2bgr]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Human_immunodeficiency_virus_1 Human immunodeficiency virus 1]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2BGR OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2BGR FirstGlance]. <br>
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</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=FUC:ALPHA-L-FUCOSE'>FUC</scene></td></tr>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2&#8491;</td></tr>
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<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[1j2e|1j2e]], [[1n1m|1n1m]], [[1nu6|1nu6]], [[1nu8|1nu8]], [[1pfq|1pfq]], [[1r9m|1r9m]], [[1rwq|1rwq]], [[1tk3|1tk3]], [[1tkr|1tkr]], [[1u8e|1u8e]], [[1w1i|1w1i]], [[2bgn|2bgn]]</div></td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=FUC:ALPHA-L-FUCOSE'>FUC</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></td></tr>
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<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Dipeptidyl-peptidase_IV Dipeptidyl-peptidase IV], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.14.5 3.4.14.5] </span></td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2bgr FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2bgr OCA], [https://pdbe.org/2bgr PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2bgr RCSB], [https://www.ebi.ac.uk/pdbsum/2bgr PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2bgr ProSAT]</span></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2bgr FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2bgr OCA], [https://pdbe.org/2bgr PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2bgr RCSB], [https://www.ebi.ac.uk/pdbsum/2bgr PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2bgr ProSAT]</span></td></tr>
</table>
</table>
== Function ==
== Function ==
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[[https://www.uniprot.org/uniprot/DPP4_HUMAN DPP4_HUMAN]] Cell surface glycoprotein receptor involved in the costimulatory signal essential for T-cell receptor (TCR)-mediated T-cell activation. Acts as a positive regulator of T-cell coactivation, by binding at least ADA, CAV1, IGF2R, and PTPRC. Its binding to CAV1 and CARD11 induces T-cell proliferation and NF-kappa-B activation in a T-cell receptor/CD3-dependent manner. Its interaction with ADA also regulates lymphocyte-epithelial cell adhesion. In association with FAP is involved in the pericellular proteolysis of the extracellular matrix (ECM), the migration and invasion of endothelial cells into the ECM. May be involved in the promotion of lymphatic endothelial cells adhesion, migration and tube formation. When overexpressed, enhanced cell proliferation, a process inhibited by GPC3. Acts also as a serine exopeptidase with a dipeptidyl peptidase activity that regulates various physiological processes by cleaving peptides in the circulation, including many chemokines, mitogenic growth factors, neuropeptides and peptide hormones. Removes N-terminal dipeptides sequentially from polypeptides having unsubstituted N-termini provided that the penultimate residue is proline.<ref>PMID:10951221</ref> <ref>PMID:17549790</ref> <ref>PMID:10570924</ref> <ref>PMID:10900005</ref> <ref>PMID:11772392</ref> <ref>PMID:14691230</ref> <ref>PMID:16651416</ref> <ref>PMID:17287217</ref> <ref>PMID:18708048</ref> [[https://www.uniprot.org/uniprot/TAT_HV1Z2 TAT_HV1Z2]] Nuclear transcriptional activator of viral gene expression, that is essential for viral transcription from the LTR promoter and replication. Acts as a sequence-specific molecular adapter, directing components of the cellular transcription machinery to the viral RNA to promote processive transcription elongation by the RNA polymerase II (RNA pol II) complex, thereby increasing the level of full-length transcripts. In the absence of Tat, the RNA Pol II generates short or non-processive transcripts that terminate at approximately 60 bp from the initiation site. Tat associates with the CCNT1/cyclin-T1 component of the P-TEFb complex (CDK9 and CCNT1), which promotes RNA chain elongation. This binding increases Tat's affinity for a hairpin structure at the 5'-end of all nascent viral mRNAs referred to as the transactivation responsive RNA element (TAR RNA) and allows Tat/P-TEFb complex to bind cooperatively to TAR RNA. The CDK9 component of P-TEFb and other Tat-activated kinases hyperphosphorylate the C-terminus of RNA Pol II that becomes stabilized and much more processive. Other factors such as HTATSF1/Tat-SF1, SUPT5H/SPT5, and HTATIP2 are also important for Tat's function. Besides its effect on RNA Pol II processivity, Tat induces chromatin remodeling of proviral genes by recruiting the histone acetyltransferases (HATs) CREBBP, EP300 and PCAF to the chromatin. This also contributes to the increase in proviral transcription rate, especially when the provirus integrates in transcriptionally silent region of the host genome. To ensure maximal activation of the LTR, Tat mediates nuclear translocation of NF-kappa-B. In this purpose, it activates EIF2AK2/PKR which, in turns, may phosphorylate and target to degradation the inhibitor IkappaB-alpha which normally retains NF-kappa-B in the cytoplasm of unstimulated cells. Through its interaction with TBP, Tat may be involved in transcription initiation as well. Interacts with the cellular capping enzyme RNGTT to mediate co-transcriptional capping of viral mRNAs. Tat protein exerts as well a positive feedback on the translation of its cognate mRNA. Tat can reactivate a latently infected cell by penetrating in it and transactivating its LTR promoter. In the cytoplasm, Tat is thought to act as a translational activator of HIV-1 mRNAs (By similarity). Extracellular circulating Tat can be endocytosed by surrounding uninfected cells via the binding to several surface receptors such as CD26, CXCR4, heparan sulfate proteoglycans (HSPG) or LDLR. Neurons are rarely infected, but they internalize Tat via their LDLR. Endosomal low pH allows Tat to cross the endosome membrane to enter the cytosol and eventually further translocate into the nucleus, thereby inducing severe cell dysfunctions ranging from cell activation to cell death. Through its interaction with nuclear HATs, Tat is potentially able to control the acetylation-dependent cellular gene expression. Tat seems to inhibit the HAT activity of KAT5/Tip60 and TAF1, and consequently modify the expression of specific cellular genes. Modulates the expression of many cellular genes involved in cell survival, proliferation or in coding for cytokines (such as IL10) or cytokine receptors. May be involved in the derepression of host interleukin IL2 expression. Mediates the activation of cyclin-dependent kinases and dysregulation of microtubule network. Tat plays a role in T-cell and neurons apoptosis. Tat induced neurotoxicity and apoptosis probably contribute to neuroAIDS. Host extracellular matrix metalloproteinase MMP1 cleaves Tat and decreases Tat's mediated neurotoxicity. Circulating Tat also acts as a chemokine-like and/or growth factor-like molecule that binds to specific receptors on the surface of the cells, affecting many cellular pathways. In the vascular system, Tat binds to ITGAV/ITGB3 and ITGA5/ITGB1 integrins dimers at the surface of endothelial cells and competes with bFGF for heparin-binding sites, leading to an excess of soluble bFGF. Binds to KDR/VEGFR-2. All these Tat-mediated effects enhance angiogenesis in Kaposi's sarcoma lesions (By similarity).
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[https://www.uniprot.org/uniprot/DPP4_HUMAN DPP4_HUMAN] Cell surface glycoprotein receptor involved in the costimulatory signal essential for T-cell receptor (TCR)-mediated T-cell activation. Acts as a positive regulator of T-cell coactivation, by binding at least ADA, CAV1, IGF2R, and PTPRC. Its binding to CAV1 and CARD11 induces T-cell proliferation and NF-kappa-B activation in a T-cell receptor/CD3-dependent manner. Its interaction with ADA also regulates lymphocyte-epithelial cell adhesion. In association with FAP is involved in the pericellular proteolysis of the extracellular matrix (ECM), the migration and invasion of endothelial cells into the ECM. May be involved in the promotion of lymphatic endothelial cells adhesion, migration and tube formation. When overexpressed, enhanced cell proliferation, a process inhibited by GPC3. Acts also as a serine exopeptidase with a dipeptidyl peptidase activity that regulates various physiological processes by cleaving peptides in the circulation, including many chemokines, mitogenic growth factors, neuropeptides and peptide hormones. Removes N-terminal dipeptides sequentially from polypeptides having unsubstituted N-termini provided that the penultimate residue is proline.<ref>PMID:10951221</ref> <ref>PMID:17549790</ref> <ref>PMID:10570924</ref> <ref>PMID:10900005</ref> <ref>PMID:11772392</ref> <ref>PMID:14691230</ref> <ref>PMID:16651416</ref> <ref>PMID:17287217</ref> <ref>PMID:18708048</ref>
== Evolutionary Conservation ==
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
[[Image:Consurf_key_small.gif|200px|right]]
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__TOC__
__TOC__
</StructureSection>
</StructureSection>
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[[Category: Dipeptidyl-peptidase IV]]
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[[Category: Homo sapiens]]
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[[Category: Human]]
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[[Category: Human immunodeficiency virus 1]]
[[Category: Large Structures]]
[[Category: Large Structures]]
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[[Category: Fan, H]]
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[[Category: Fan H]]
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[[Category: Liu, J]]
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[[Category: Liu J]]
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[[Category: Reutter, W]]
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[[Category: Reutter W]]
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[[Category: Saenger, W]]
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[[Category: Saenger W]]
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[[Category: Weihofen, W A]]
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[[Category: Weihofen WA]]
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[[Category: Alpha/beta-hydrolase fold]]
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[[Category: Beta-propeller fold]]
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[[Category: Dppiv]]
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[[Category: Hydrolase]]
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[[Category: Hydrolase-complex]]
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Current revision

Crystal structure of HIV-1 Tat derived nonapeptides Tat(1-9) bound to the active site of Dipeptidyl peptidase IV (CD26)

PDB ID 2bgr

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Proteopedia Page Contributors and Editors (what is this?)

OCA

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