3btb
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| - | {{STRUCTURE_3btb| PDB=3btb | SCENE= }} | ||
| - | ===NMR SOLUTION STRUCTURE OF A BAND 3 PEPTIDE INHIBITOR BOUND TO GLYCERALDEHYDE-3-PHOSPHATE DEHYDROGENASE, 20 STRUCTURES=== | ||
| - | {{ABSTRACT_PUBMED_9454576}} | ||
| - | == | + | ==NMR SOLUTION STRUCTURE OF A BAND 3 PEPTIDE INHIBITOR BOUND TO GLYCERALDEHYDE-3-PHOSPHATE DEHYDROGENASE, 20 STRUCTURES== |
| - | [[http://www.uniprot.org/uniprot/B3AT_HUMAN B3AT_HUMAN | + | <StructureSection load='3btb' size='340' side='right'caption='[[3btb]]' scene=''> |
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[3btb]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3BTB OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3BTB FirstGlance]. <br> | ||
| + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR, 20 models</td></tr> | ||
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NH2:AMINO+GROUP'>NH2</scene></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=3btb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3btb OCA], [https://pdbe.org/3btb PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3btb RCSB], [https://www.ebi.ac.uk/pdbsum/3btb PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3btb ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == Disease == | ||
| + | [https://www.uniprot.org/uniprot/B3AT_HUMAN B3AT_HUMAN] Defects in SLC4A1 are the cause of elliptocytosis type 4 (EL4) [MIM:[https://omim.org/entry/109270 109270]. EL4 is a Rhesus-unlinked form of hereditary elliptocytosis, a genetically heterogeneous, autosomal dominant hematologic disorder. It is characterized by variable hemolytic anemia and elliptical or oval red cell shape.<ref>PMID:1722314</ref> <ref>PMID:1538405</ref> Defects in SLC4A1 are the cause of spherocytosis type 4 (SPH4) [MIM:[https://omim.org/entry/612653 612653]; also known as hereditary spherocytosis type 4 (HS4). Spherocytosis is a hematologic disorder leading to chronic hemolytic anemia and characterized by numerous abnormally shaped erythrocytes which are generally spheroidal.<ref>PMID:8547122</ref> <ref>PMID:1378323</ref> <ref>PMID:7530501</ref> <ref>PMID:8943874</ref> <ref>PMID:8640229</ref> <ref>PMID:9207478</ref> <ref>PMID:9012689</ref> <ref>PMID:9233560</ref> <ref>PMID:9973643</ref> <ref>PMID:10580570</ref> <ref>PMID:10942416</ref> <ref>PMID:10745622</ref> <ref>PMID:11380459</ref> <ref>PMID:15813913</ref> <ref>PMID:16227998</ref> Defects in SLC4A1 are the cause of renal tubular acidosis, distal, autosomal dominant (AD-dRTA) [MIM:[https://omim.org/entry/179800 179800]. A disease characterized by reduced ability to acidify urine, variable hyperchloremic hypokalemic metabolic acidosis, nephrocalcinosis, and nephrolithiasis. Defects in SLC4A1 are the cause of renal tubular acidosis, distal, with hemolytic anemia (dRTA-HA) [MIM:[https://omim.org/entry/611590 611590]. A disease characterized by the association of hemolytic anemia with distal renal tubular acidosis, the reduced ability to acidify urine resulting in variable hyperchloremic hypokalemic metabolic acidosis, nephrocalcinosis, and nephrolithiasis. Defects in SLC4A1 are the cause of renal tubular acidosis, distal, with normal red cell morphology (dRTA-NRC) [MIM:[https://omim.org/entry/611590 611590]. A disease characterized by reduced ability to acidify urine, variable hyperchloremic hypokalemic metabolic acidosis, nephrocalcinosis, and nephrolithiasis. | ||
| + | == Function == | ||
| + | [https://www.uniprot.org/uniprot/B3AT_HUMAN B3AT_HUMAN] Band 3 is the major integral glycoprotein of the erythrocyte membrane. Band 3 has two functional domains. Its integral domain mediates a 1:1 exchange of inorganic anions across the membrane, whereas its cytoplasmic domain provides binding sites for cytoskeletal proteins, glycolytic enzymes, and hemoglobin. | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | A protein-protein association regulated by phosphorylation of tyrosine is examined by NMR structural studies and biochemical studies. Binding of glyceraldehyde-3-phosphate dehydrogenase (G3PDH) and aldolase to the N-terminus of human erythrocyte anion transporter, band 3, inhibits enzyme activity. This inhibition is reversed upon phosphorylation of band 3 Y8, as shown by kinetic studies on purified components, as well as in vivo studies. Thus, tyrosine phosphorylation mediates against the intermolecular protein-protein association, in contrast to the positive control involving SH2 and PTB domains where phosphorylation is required for binding. To elucidate the basis of recognition and negative control by tyrosine phosphorylation, the structure of a synthetic peptide, B3P, corresponding to the first 15 residues of band 3 (MEELQDDYEDMMEEN-NH2), bound to G3PDH has been determined using the exchange-transferred nuclear Overhauser effect. The G3PDH-bound B3P structure was found to be very similar to the structure recognized by aldolase. A hydrophobic triad forms from side chains within a loop structure of residues 4 through 9 in both bound species. Another structural feature stabilizing the loop, in the case of the B3P-G3PDH complex, is a hydrogen bond between the side chains of Y8 and D10 associated with a beta-turn of residues 8-11. Based on the structure of this phosphorylation sensitive interaction (PSI) loop, it is suggested that tyrosine phosphorylation disrupts protein-protein association, in part, by intramolecular electrostatic destabilization. The inhibition by B3P is competitive with respect to the coenzyme NAD+ and noncompetitive with the substrate analog arsenate. Specific binding of B3P to G3PDH is demonstrated by reversion of the NMR spectral properties of bound B3P to those of the free peptide upon addition of coenzyme and substrate analog. The stoichiometry of binding for the B3P-G3PDH complex was determined from Sephadex G-50 displacement experiments to be 4:1. Collectively, these results are consistent with B3P binding the active site of G3PDH. | ||
| - | + | Insights into tyrosine phosphorylation control of protein-protein association from the NMR structure of a band 3 peptide inhibitor bound to glyceraldehyde-3-phosphate dehydrogenase.,Eisenmesser EZ, Post CB Biochemistry. 1998 Jan 20;37(3):867-77. PMID:9454576<ref>PMID:9454576</ref> | |
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| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | + | </div> | |
| - | + | <div class="pdbe-citations 3btb" style="background-color:#fffaf0;"></div> | |
| - | == | + | == References == |
| - | <references | + | <references/> |
| + | __TOC__ | ||
| + | </StructureSection> | ||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
| - | [[Category: | + | [[Category: Large Structures]] |
| - | [[Category: | + | [[Category: Eisenmesser EZ]] |
| - | [[Category: | + | [[Category: Post CB]] |
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Current revision
NMR SOLUTION STRUCTURE OF A BAND 3 PEPTIDE INHIBITOR BOUND TO GLYCERALDEHYDE-3-PHOSPHATE DEHYDROGENASE, 20 STRUCTURES
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