5m6z

From Proteopedia

(Difference between revisions)

Revision as of 07:04, 12 December 2018

The X-ray structure of human M189I PGK-1 mutant in partially closed conformation

Structural highlights

5m6z is a 1 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	, , ,
Gene:	PGK1, PGKA, MIG10, OK/SW-cl.110 (HUMAN)
Activity:	Phosphoglycerate kinase, with EC number 2.7.2.3
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

[PGK1_HUMAN] Defects in PGK1 are the cause of phosphoglycerate kinase 1 deficiency (PGK1D) [MIM:300653]. It is a condition with a highly variable clinical phenotype that includes hemolytic anemia, rhabdomyolysis, myopathy and neurologic involvement. Patients can express one or more of these manifestations.^[1] ^[2] ^[3] ^[4] ^[5] ^[6] ^[7] ^[8] ^[9]

Function

[PGK1_HUMAN] In addition to its role as a glycolytic enzyme, it seems that PGK-1 acts as a polymerase alpha cofactor protein (primer recognition protein).

Publication Abstract from PubMed

Cancer cells are able to survive in difficult conditions, reprogramming their metabolism according to their requirements. Under hypoxic conditions they shift from oxidative phosphorylation to aerobic glycolysis, a behavior known as Warburg effect. In the last years, glycolytic enzymes have been identified as potential targets for alternative anticancer therapies. Recently, phosphoglycerate kinase 1 (PGK1), an ubiquitous enzyme expressed in all somatic cells that catalyzes the seventh step of glycolysis which consists of the reversible phosphotransfer reaction from 1,3-bisphosphoglycerate to ADP, has been discovered to be overexpressed in many cancer types. Moreover, several somatic variants of PGK1 have been identified in tumors. In this study we analyzed the effect of the single nucleotide variants found in cancer tissues on the PGK1 structure and function. Our results clearly show that the variants display a decreased catalytic efficiency and/or thermodynamic stability and an altered local tertiary structure, as shown by the solved X-ray structures. The changes in the catalytic properties and in the stability of the PGK1 variants, mainly due to the local changes evidenced by the X-ray structures, suggest also changes in the functional role of PGK to support the biosynthetic need of the growing and proliferating tumour cells.

The phosphoglycerate kinase 1 variants found in carcinoma cells display different catalytic activity and conformational stability compared to the native enzyme.,Fiorillo A, Petrosino M, Ilari A, Pasquo A, Cipollone A, Maggi M, Chiaraluce R, Consalvi V PLoS One. 2018 Jul 11;13(7):e0199191. doi: 10.1371/journal.pone.0199191., eCollection 2018. PMID:29995887^[10]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Yoshida A, Twele TW, Dave V, Beutler E. Molecular abnormality of a phosphoglycerate kinase variant (PGK-Alabama). Blood Cells Mol Dis. 1995;21(3):179-81. PMID:8673469 doi:S1079-9796(85)70020-4
↑ Cohen-Solal M, Valentin C, Plassa F, Guillemin G, Danze F, Jaisson F, Rosa R. Identification of new mutations in two phosphoglycerate kinase (PGK) variants expressing different clinical syndromes: PGK Creteil and PGK Amiens. Blood. 1994 Aug 1;84(3):898-903. PMID:8043870
↑ Ookawara T, Dave V, Willems P, Martin JJ, de Barsy T, Matthys E, Yoshida A. Retarded and aberrant splicings caused by single exon mutation in a phosphoglycerate kinase variant. Arch Biochem Biophys. 1996 Mar 1;327(1):35-40. PMID:8615693 doi:http://dx.doi.org/10.1006/abbi.1996.0089
↑ Valentin C, Birgens H, Craescu CT, Brodum-Nielsen K, Cohen-Solal M. A phosphoglycerate kinase mutant (PGK Herlev; D285V) in a Danish patient with isolated chronic hemolytic anemia: mechanism of mutation and structure-function relationships. Hum Mutat. 1998;12(4):280-7. PMID:9744480 doi:<280::AID-HUMU10>3.0.CO;2-V 10.1002/(SICI)1098-1004(1998)12:4<280::AID-HUMU10>3.0.CO;2-V
↑ Maeda M, Yoshida A. Molecular defect of a phosphoglycerate kinase variant (PGK-Matsue) associated with hemolytic anemia: Leu----Pro substitution caused by T/A----C/G transition in exon 3. Blood. 1991 Mar 15;77(6):1348-52. PMID:2001457
↑ Maeda M, Bawle EV, Kulkarni R, Beutler E, Yoshida A. Molecular abnormalities of a phosphoglycerate kinase variant generated by spontaneous mutation. Blood. 1992 May 15;79(10):2759-62. PMID:1586722
↑ Fujii H, Kanno H, Hirono A, Shiomura T, Miwa S. A single amino acid substitution (157 Gly----Val) in a phosphoglycerate kinase variant (PGK Shizuoka) associated with chronic hemolysis and myoglobinuria. Blood. 1992 Mar 15;79(6):1582-5. PMID:1547346
↑ Fujii H, Chen SH, Akatsuka J, Miwa S, Yoshida A. Use of cultured lymphoblastoid cells for the study of abnormal enzymes: molecular abnormality of a phosphoglycerate kinase variant associated with hemolytic anemia. Proc Natl Acad Sci U S A. 1981 Apr;78(4):2587-90. PMID:6941312
↑ Fujii H, Yoshida A. Molecular abnormality of phosphoglycerate kinase-Uppsala associated with chronic nonspherocytic hemolytic anemia. Proc Natl Acad Sci U S A. 1980 Sep;77(9):5461-5. PMID:6933565
↑ Fiorillo A, Petrosino M, Ilari A, Pasquo A, Cipollone A, Maggi M, Chiaraluce R, Consalvi V. The phosphoglycerate kinase 1 variants found in carcinoma cells display different catalytic activity and conformational stability compared to the native enzyme. PLoS One. 2018 Jul 11;13(7):e0199191. doi: 10.1371/journal.pone.0199191., eCollection 2018. PMID:29995887 doi:http://dx.doi.org/10.1371/journal.pone.0199191

1 Structural highlights
2 Disease
3 Function
4 Publication Abstract from PubMed
5 See Also
6 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/5m6z"

@@ Line 3: / Line 3: @@
 <StructureSection load='5m6z' size='340' side='right' caption='[[5m6z]], [[Resolution|resolution]] 1.67&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[5m6z]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5M6Z OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5M6Z FirstGlance]. <br>
+<table><tr><td colspan='2'>[[5m6z]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5M6Z OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5M6Z FirstGlance]. <br>
 </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=3PG:3-PHOSPHOGLYCERIC+ACID'>3PG</scene>, <scene name='pdbligand=ADP:ADENOSINE-5-DIPHOSPHATE'>ADP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene></td></tr>
+<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">PGK1, PGKA, MIG10, OK/SW-cl.110 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
 <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Phosphoglycerate_kinase Phosphoglycerate kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.2.3 2.7.2.3] </span></td></tr>
 <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5m6z FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5m6z OCA], [http://pdbe.org/5m6z PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5m6z RCSB], [http://www.ebi.ac.uk/pdbsum/5m6z PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5m6z ProSAT]</span></td></tr>
@@ Line 12: / Line 13: @@
 == Function ==
 [[http://www.uniprot.org/uniprot/PGK1_HUMAN PGK1_HUMAN]] In addition to its role as a glycolytic enzyme, it seems that PGK-1 acts as a polymerase alpha cofactor protein (primer recognition protein).
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+Cancer cells are able to survive in difficult conditions, reprogramming their metabolism according to their requirements. Under hypoxic conditions they shift from oxidative phosphorylation to aerobic glycolysis, a behavior known as Warburg effect. In the last years, glycolytic enzymes have been identified as potential targets for alternative anticancer therapies. Recently, phosphoglycerate kinase 1 (PGK1), an ubiquitous enzyme expressed in all somatic cells that catalyzes the seventh step of glycolysis which consists of the reversible phosphotransfer reaction from 1,3-bisphosphoglycerate to ADP, has been discovered to be overexpressed in many cancer types. Moreover, several somatic variants of PGK1 have been identified in tumors. In this study we analyzed the effect of the single nucleotide variants found in cancer tissues on the PGK1 structure and function. Our results clearly show that the variants display a decreased catalytic efficiency and/or thermodynamic stability and an altered local tertiary structure, as shown by the solved X-ray structures. The changes in the catalytic properties and in the stability of the PGK1 variants, mainly due to the local changes evidenced by the X-ray structures, suggest also changes in the functional role of PGK to support the biosynthetic need of the growing and proliferating tumour cells.
+The phosphoglycerate kinase 1 variants found in carcinoma cells display different catalytic activity and conformational stability compared to the native enzyme.,Fiorillo A, Petrosino M, Ilari A, Pasquo A, Cipollone A, Maggi M, Chiaraluce R, Consalvi V PLoS One. 2018 Jul 11;13(7):e0199191. doi: 10.1371/journal.pone.0199191., eCollection 2018. PMID:29995887<ref>PMID:29995887</ref>
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
+</div>
+<div class="pdbe-citations 5m6z" style="background-color:#fffaf0;"></div>
+==See Also==
+*[[Phosphoglycerate Kinase|Phosphoglycerate Kinase]]
 == References ==
 <references/>
 __TOC__
 </StructureSection>
+[[Category: Human]]
 [[Category: Phosphoglycerate kinase]]
 [[Category: Cipollone, A]]

5m6z

From Proteopedia

Revision as of 07:04, 12 December 2018

The X-ray structure of human M189I PGK-1 mutant in partially closed conformation

Structural highlights

Disease

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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