phosphoglycerate kinase

WordNet

1. an enzyme that catalyzes the conversion of a proenzyme to an active enzyme
2. the basic unit of money in Papua New Guinea

Wikipedia preview

出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2016/07/27 05:43:49」(JST)

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Phosphoglycerate kinase
Identifiers
EC number	2.7.2.3
CAS number	9001-83-6
Databases
IntEnz	IntEnz view
BRENDA	BRENDA entry
ExPASy	NiceZyme view
KEGG	KEGG entry
MetaCyc	metabolic pathway
PRIAM	profile
PDB structures	RCSB PDB PDBe PDBsum
Gene Ontology	AmiGO / EGO
Search PMC articles PubMed articles NCBI proteins

Phosphoglycerate kinase
Structure of yeast phosphoglycerate kinase.
Identifiers
Symbol	PGK
Pfam	PF00162
InterPro	IPR001576
PROSITE	PDOC00102
SCOP	3pgk
SUPERFAMILY	3pgk
Available protein structures: Pfam structures PDB RCSB PDB; PDBe; PDBj PDBsum structure summary

Phosphoglycerate kinase (EC 2.7.2.3) (PGK) is an enzyme that catalyzes the reversible transfer of a phosphate group from 1,3-bisphosphoglycerate (1,3-BPG) to ADP producing 3-phosphoglycerate (3-PG) and ATP. Like all kinases it is a transferase. PGK is a major enzyme used in glycolysis, in the first ATP-generating step of the glycolytic pathway. In gluconeogenesis, the reaction catalyzed by PGK proceeds in the opposite direction, generating ADP and 1,3-BPG.

In humans, two isozymes of PGK have been so far identified, PGK1 and PGK2. The isozymes have 87-88% identical amino acid sequence identity and though they are structurally and functionally similar, they have different localizations: PGK2, encoded by an autosomal gene, is unique to meiotic and postmeiotic spermatogenic cells, while PGK1, encoded on the X-chromosome, is ubiquitously expressed in all cells.

Biological function

Diagram showing glycolytic and gluconeogenic pathways. Note that phosphoglycerate kinase is used in both directions.

PGK is present in all living organisms as one of the two ATP-generating enzymes in glycolysis. In the gluconeogenic pathway, PGK catalyzes the reverse reaction. Under biochemical standard conditions, the glycolytic direction is favored.

In the Calvin cycle in photosynthetic organisms, PGK catalyzes the phosphorylation of 3-PG, producing 1,3-BPG and ADP, as part of the reactions that regenerate ribulose-1,5-bisphosphate.

PGK has been reported to exhibit thiol reductase activity on plasmin, leading to angiostatin formation, which inhibits angiogenesis and tumor growth. The enzyme was also shown to participate in DNA replication and repair in mammal cell nuclei.

The human isozyme PGK2, which is only expressed during spermatogenesis, was shown to be essential for sperm function in mice.

Interactive pathway map

Click on genes, proteins and metabolites below to link to respective articles.

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|{{{bSize}}}px|alt=Glycolysis and Gluconeogenesis edit]]

File:WP534.png

Glycolysis and Gluconeogenesis edit

Structure

Overview

PGK is found in all living organisms and its sequence has been highly conserved throughout evolution. The enzyme exists as a 415-residue monomer containing two nearly equal-sized domains that correspond to the N- and C-termini of the protein. 3-phosphoglycerate (3-PG) binds to the N-terminal, while the nucleotide substrates, MgATP or MgADP, bind to the C-terminal domain of the enzyme. This extended two-domain structure is associated with large-scale 'hinge-bending' conformational changes, similar to those found in hexokinase. The two domains of the protein are separated by a cleft and linked by two alpha-helices. At the core of each domain is a 6-stranded parallel beta-sheet surrounded by alpha helices. The two lobes are capable of folding independently, consistent with the presence of intermediates on the folding pathway with a single domain folded. Though the binding of either substrate triggers a conformational change, only through the binding of both substrates does domain closure occur, leading to the transfer of the phosphate group.

The enzyme has a tendency to exist in the open conformation with short periods of closure and catalysis, which allow for rapid diffusion of substrate and products through the binding sites; the open conformation of PGK is more conformationally stable due to the exposure of a hydrophobic region of the protein upon domain closure.

Role of magnesium

Magnesium ions are normally complexed to the phosphate groups the nucleotide substrates of PGK. It is known that in the absence of magnesium, no enzyme activity occurs. The bivalent metal assists the enzyme ligands in shielding the bound phosphate group's negative charges, allowing the nucleophilic attack to occur; this charge-stabilization is a typical characteristic of phosphotransfer reaction. It is theorized that the ion may also encourage domain closure when PGK has bound both substrates.

Mechanism

Phosphoglycerate kinase mechanism in glycolysis.

Without either substrate bound, PGK exists in an "open" conformation. After both the triose and nucleotide substrates are bound to the N- and C-terminal domains, respectively, an extensive hinge-bending motion occurs, bringing the domains and their bound substrates into close proximity and leading to a "closed" conformation. Then, in the case of the forward glycolytic reaction, the beta-phosphate of ADP initiates a nucleophilic attack on the 1-phosphate of 1,3-BPG. The Lys219 on the enzyme guides the phosphate group to the substrate.

PGK proceeds through a charge-stabilized transition state that is favored over the arrangement of the bound substrate in the closed enzyme because in the transition state, all three phosphate oxygens are stabilized by ligands, as opposed to only two stabilized oxygens in the initial bound state.

In the glycolytic pathyway, 1,3-BPG is the phosphate donor and has a high phosphoryl-transfer potential. The PGK-catalyzed transfer of the phosphate group from 1,3-BPG to ADP to yield ATP can power the carbon-oxidation reaction of the previous glycolytic step (converting glyceraldehyde 3-phosphate to 3-phosphoglycerate).

Regulation

The enzyme is activated by low concentrations of various multivalent anions, such as pyrophosphate, sulfate, phosphate, and citrate. High concentrations of MgATP and 3-PG activates PGK, while Mg2+ at high concentrations non-competitively inhibits the enzyme.

PGK exhibits a wide specificity toward nucleotide substrates. Its activity is inhibited by salicylates, which appear to mimic the enzyme's nucleotide substrate.

Macromolecular crowding has been shown to increase PGK activity in both computer simluations and in vitro environments simulating a cell interior; as a result of crowding, the enzyme becomes more enyzmatically active and more compact.

Disease relevance

Phosphoglycerate kinase (PGK) deficiency is an X-linked recessive trait associated with hemolytic anemia, mental disorders and myopathy in humans. Since the trait is X-linked, it is usually fully expressed in males, who have one X chromosome; affected females are typically asymptomatic. The condition results from mutations in Pgk1, the gene encoding PGK1, and twenty mutations have been identified. On a molecular level, the mutation in Pgk1 impairs the thermal stability and inhibits the catalytic activity of the enzyme. PGK is the only enzyme in the immediate glycolytic pathway encoded by an X-linked gene. In the case of hemolytic anemia, PGK deficiency occurs in the erythrocytes. Currently, no definitive treatment exists for PGK deficiency.

PGK1 overexpression has been associated with gastric cancer and has been found to increase the invasiveness of gastric cancer cells in vitro. The enzyme is secreted by tumor cells and participates in the angiogenic process, leading to the release of angiostatin and the inhibition of tumor blood vessel growth.

Due to its wide specificity towards nucleotide substrates, PGK is known to participate in the phosphorylation and activation of HIV antiretroviral drugs, which are nucleotide-based.

Human isozymes

phosphoglycerate kinase 1 Identifiers Symbol PGK1 Entrez 5230 HUGO 8896 OMIM 311800 RefSeq NM_000291 UniProt P00558 Other data EC number 2.7.2.3 Locus Chr. X q13.3

phosphoglycerate kinase 2 Identifiers Symbol PGK2 Entrez 5232 HUGO 8898 OMIM 172270 RefSeq NM_138733 UniProt P07205 Other data EC number 2.7.2.3 Locus Chr. 6 p21-q12

References

External links

• -858783685 at GPnotebook
• Phosphoglycerate kinase at the US National Library of Medicine Medical Subject Headings (MeSH)
• Illustration at arizona.edu

This article incorporates text from the public domain Pfam and InterPro IPR001576

UpToDate Contents

全文を閲覧するには購読必要です。 To read the full text you will need to subscribe.

• 1. ホスホグリセリン酸キナーゼ欠損症およびホスホグリセリン酸ムターゼ欠損症 phosphoglycerate kinase deficiency and phosphoglycerate mutase deficiency
• 2. 成人における血栓性血小板減少性紫斑病-溶血性尿毒症症候群の治療および予後 neuroacanthocytosis
• 3. 成人におけるフィラデルフィア染色体陽性急性リンパ芽球性白血病に対する導入療法 induction therapy for philadelphia chromosome positive acute lymphoblastic leukemia in adults
• 4. 心筋障害のバイオマーカーとしてのトロポニンおよびクレアチンキナーゼ troponins and creatine kinase as biomarkers of cardiac injury
• 5. 分子標的薬である血管新生阻害剤の毒性：心血管系への影響 toxicity of molecularly targeted antiangiogenic agents cardiovascular effects

English Journal

• Binding of group B streptococcal phosphoglycerate kinase to plasminogen and actin.

• Boone TJ, Burnham CA, Tyrrell GJ.SourceThe Department of Laboratory Medicine and Pathology, The University of Alberta, Edmonton, Alberta, Canada. T.Boone@provlab.ab.ca
• Microbial pathogenesis.Microb Pathog.2011 Oct;51(4):255-61. Epub 2011 Jun 28.
• The glycolytic enzyme, phosphoglycerate kinase (PGK) of group B streptococci (GBS), has previously been identified as expressed on the GBS cell surface. The data presented describes the ability of group B streptococcal phosphoglycerate kinase (GBS-PGK) to bind to plasminogen and to bind actin. GBS-P
• PMID 21729749

Japanese Journal

• Redox Control of the Activity of Phosphoglycerate Kinase in Synechocystis sp. PCC6803

• TSUKAMOTO Yu,FUKUSHIMA Yuriko,HARA Satoshi,HISABORI Toru
• Plant and cell physiology 54(4), 484-491, 2013-04-01
• NAID 10031163842

• Redox Control of the Activity of Phosphoglycerate Kinase in Synechocystis sp. PCC6803

• Tsukamoto Yu,Fukushima Yuriko,Hara Satoshi [他]
• Plant and cell physiology 54(4), 484-491, 2013-04
• NAID 40019643139

Related Pictures

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★リンクテーブル★

リンク元	「解糖系」「ホスホグリセリン酸キナーゼ」「PGK deficiency」「PGK」
拡張検索	「muscle phosphoglycerate kinase deficiency syndrome」「phosphoglycerate kinase欠乏症」
関連記事	「kinase」「phosphoglycerate」

「解糖系」

　　[★]

英

glycolytic pathway

同

エムデン-マイヤーホフ経路 Embden-Meyerhof pathway

関

解糖、TCA回路

• CH(OH)-CH(OH)-C(OH)H-CH(OH)-C(CH2OH)H-O- グルコース (OHが↓↓↑↓↑)
• CH(OH)-CH(OH)-C(OH)H-CH(OH)-C(CH2O-PO3)H-O- グルコース-6-リン酸 (OHが↓↓↑↓↑)
• C(CH2OH)OH-C(OH)H-CH(OH)-C(CH2O-PO3)H-O- フルクトース-6-リン酸
• C(CH2O-PO3)OH-C(OH)H-CH(OH)-C(CH2O-PO3)H-O- フルクトース-1,6-リン酸

glucose
↓-hexokinase/glucokinase(liver)
glucose 6-phosphate
↓-phosphohexose isomerase
fructose 6-phosphate
↓-phosphofructokinase
fructose 1,6-bisphosphate
↓-aldolase
glyceraldehyde 3-phosphate
↓-glyceraldehyde-3-phosphate dehydrogenase
1,3-bisphosphoglycerate
↓-phosphoglycerate kinase →ATP
3-phosphoglycerate
↓-phosphoglyceate mutase
2-phosphoglycerate
↓-enolase
phosphoenolpyruvate
↓-pyruvate kinase → ATP
pyruvate
　－(pyruvate dehydrogenase)→acetyl-CoA
　－(pyruvate carboxylase)→oxaloacetate－(NADH+H+)→malate

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解糖系の酵素 (first aid step1 2006 p.87, FASTEP1_87_酵素一覧.xls)

1	galactokinase	キナーゼ
2	galactose-1-phosphate uridyltransferase	転移酵素
3	hexokinase/glucokinase	キナーゼ
4	glucose-6-phosphatase	ホスファターゼ
5	glucose-6-phosphate dehydrogenase	脱水素酵素
6	transketolase
7	phosphofructokinase	キナーゼ
8	fructose-1,6-bisphosphatase	ホスファターゼ
9	fructokinase	キナーゼ	フルクトキナーゼ
10	aldolase B		アルドラーゼ
11	pyruvate kinase	キナーゼ	ピルビン酸キナーゼ
12	pyruvate dehydrogenase	脱水素酵素	ピルビン酸デヒドロゲナーゼ
13	HMG-CoA reductase	還元酵素	HMG-CoA還元酵素
14	pyruvate carboxylase	カルボキシラーゼ	ピルビン酸カルボキシラーゼ
15	PEP carboxykinase	キナーゼ	PEPカルボキシキナーゼ
16	citrate synthase	合成酵素	クエン酸合成酵素
17	α-ketoglutarate dehydrogenase	脱水素酵素	α-ケトグルタミン酸脱水素酵素
18	ornithine transcarbamylase	転移酵素	オルニチンカルバモイルトランスフェラーゼ

「ホスホグリセリン酸キナーゼ」

　　[★]

英

phosphoglycerate kinase, PGK

「PGK deficiency」

　　[★]

同

phosphoglycerate kinase

「PGK」

　　[★]

同

phosphoglycerate kinase

「muscle phosphoglycerate kinase deficiency syndrome」

　　[★] 筋ホスホグリセリン酸キナーゼ欠損症候群

「phosphoglycerate kinase欠乏症」

　　[★] ホスホグリセリン酸キナーゼ欠損症

「kinase」

　　[★] キナーゼ カイネース リン酸化酵素 phosphoenzyme phosphotransferase 　

「phosphoglycerate」

　　[★]

ホスホグリセリン酸