2vgb: Difference between revisions

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</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=2vgb ConSurf].
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=2vgb ConSurf].
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== Publication Abstract from PubMed ==
Deficiency of human erythrocyte isozyme (RPK) is, together with glucose-6-phosphate dehydrogenase deficiency, the most common cause of the nonspherocytic hemolytic anemia. To provide a molecular framework to the disease, we have solved the 2.7 A resolution crystal structure of human RPK in complex with fructose 1,6-bisphosphate, the allosteric activator, and phosphoglycolate, a substrate analogue, and we have functionally and structurally characterized eight mutants (G332S, G364D, T384M, D390N, R479H, R486W, R504L, and R532W) found in RPK-deficient patients. The mutations target distinct regions of RPK structure, including domain interfaces and catalytic and allosteric sites. The mutations affect to a different extent thermostability, catalytic efficiency, and regulatory properties. These studies are the first to correlate the clinical symptoms with the molecular properties of the mutant enzymes. Mutations greatly impairing thermostability and/or activity are associated with severe anemia. Some mutant proteins exhibit moderate changes in the kinetic parameters, which are sufficient to cause mild to severe anemia, underlining the crucial role of RPK for erythrocyte metabolism. Prediction of the effects of mutations is difficult because there is no relation between the nature and location of the replaced amino acid and the type of molecular perturbation. Characterization of mutant proteins may serve as a valuable tool to assist with diagnosis and genetic counseling.
Structure and function of human erythrocyte pyruvate kinase. Molecular basis of nonspherocytic hemolytic anemia.,Valentini G, Chiarelli LR, Fortin R, Dolzan M, Galizzi A, Abraham DJ, Wang C, Bianchi P, Zanella A, Mattevi A J Biol Chem. 2002 Jun 28;277(26):23807-14. Epub 2002 Apr 17. PMID:11960989<ref>PMID:11960989</ref>
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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==See Also==
==See Also==

Latest revision as of 10:07, 1 May 2024

HUMAN ERYTHROCYTE PYRUVATE KINASEHUMAN ERYTHROCYTE PYRUVATE KINASE

Structural highlights

2vgb is a 4 chain structure with sequence from Homo sapiens. This structure supersedes the now removed PDB entry 1liu. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 2.73Å
Ligands:, , ,
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

KPYR_HUMAN Defects in PKLR are the cause of pyruvate kinase hyperactivity (PKHYP) [MIM:102900; also known as high red cell ATP syndrome. This autosomal dominant phenotype is characterized by increase of red blood cell ATP.[1] Defects in PKLR are the cause of pyruvate kinase deficiency of red cells (PKRD) [MIM:266200. A frequent cause of hereditary non-spherocytic hemolytic anemia. Clinically, pyruvate kinase-deficient patients suffer from a highly variable degree of chronic hemolysis, ranging from severe neonatal jaundice and fatal anemia at birth, severe transfusion-dependent chronic hemolysis, moderate hemolysis with exacerbation during infection, to a fully compensated hemolysis without apparent anemia.

Function

KPYR_HUMAN Plays a key role in glycolysis (By similarity).

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

See Also

References

  1. ↑ Beutler E, Westwood B, van Zwieten R, Roos D. G-->T transition at cDNA nt 110 (K37Q) in the PKLR (pyruvate kinase) gene is the molecular basis of a case of hereditary increase of red blood cell ATP. Hum Mutat. 1997;9(3):282-5. PMID:9090535 doi:<282::AID-HUMU13>3.0.CO;2-Z 10.1002/(SICI)1098-1004(1997)9:3<282::AID-HUMU13>3.0.CO;2-Z

2vgb, resolution 2.73Å

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