Phosphoglycerate dehydrogenase: Difference between revisions

Latest revision as of 10:56, 27 August 2023

Function

Phosphoglycerate dehydrogenase (PGDH) catalyzes the conversion of 3-phosphoglycerate into 3-phosphohydroxypyruvate. This is the first step of serine biosynthesis^[1]. NAD is used as cofactor.

Relevance

In some cancer cells there is an elevation in PGDH level and hence an increase in serine biosynthesis^[2].

Structural highlights

The active site of Mycobacterium tuberculosis PGDH located in the cleft between the substrate and the NAD-binding domains contains the ^[3].

See Rossmann fold.

Phosphoglycerate dehydrogenase complex with hydroxypyruvic acid phosphate and tartarate (PDB entry 3ddn)

Drag the structure with the mouse to rotate

3D structures of phosphoglycerate dehydrogenase3D structures of phosphoglycerate dehydrogenase

Updated on 27-August-2023

ReferencesReferences

↑ Yamasaki M, Yamada K, Furuya S, Mitoma J, Hirabayashi Y, Watanabe M. 3-Phosphoglycerate dehydrogenase, a key enzyme for l-serine biosynthesis, is preferentially expressed in the radial glia/astrocyte lineage and olfactory ensheathing glia in the mouse brain. J Neurosci. 2001 Oct 1;21(19):7691-704. PMID:11567059
↑ Mullarky E, Lucki NC, Beheshti Zavareh R, Anglin JL, Gomes AP, Nicolay BN, Wong JC, Christen S, Takahashi H, Singh PK, Blenis J, Warren JD, Fendt SM, Asara JM, DeNicola GM, Lyssiotis CA, Lairson LL, Cantley LC. Identification of a small molecule inhibitor of 3-phosphoglycerate dehydrogenase to target serine biosynthesis in cancers. Proc Natl Acad Sci U S A. 2016 Feb 16;113(7):1778-83. doi:, 10.1073/pnas.1521548113. Epub 2016 Feb 1. PMID:26831078 doi:http://dx.doi.org/10.1073/pnas.1521548113
↑ Dey S, Burton RL, Grant GA, Sacchettini JC. Structural analysis of substrate and effector binding in Mycobacterium tuberculosis D-3-phosphoglycerate dehydrogenase. Biochemistry. 2008 Aug 12;47(32):8271-82. Epub 2008 Jul 16. PMID:18627175 doi:10.1021/bi800212b

Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

Michal Harel, Alexander Berchansky, Joel L. Sussman

[1] Yamasaki M, Yamada K, Furuya S, Mitoma J, Hirabayashi Y, Watanabe M. 3-Phosphoglycerate dehydrogenase, a key enzyme for l-serine biosynthesis, is preferentially expressed in the radial glia/astrocyte lineage and olfactory ensheathing glia in the mouse brain. J Neurosci. 2001 Oct 1;21(19):7691-704. PMID:11567059

[2] Mullarky E, Lucki NC, Beheshti Zavareh R, Anglin JL, Gomes AP, Nicolay BN, Wong JC, Christen S, Takahashi H, Singh PK, Blenis J, Warren JD, Fendt SM, Asara JM, DeNicola GM, Lyssiotis CA, Lairson LL, Cantley LC. Identification of a small molecule inhibitor of 3-phosphoglycerate dehydrogenase to target serine biosynthesis in cancers. Proc Natl Acad Sci U S A. 2016 Feb 16;113(7):1778-83. doi:, 10.1073/pnas.1521548113. Epub 2016 Feb 1. PMID:26831078 doi:http://dx.doi.org/10.1073/pnas.1521548113

[3] Dey S, Burton RL, Grant GA, Sacchettini JC. Structural analysis of substrate and effector binding in Mycobacterium tuberculosis D-3-phosphoglycerate dehydrogenase. Biochemistry. 2008 Aug 12;47(32):8271-82. Epub 2008 Jul 16. PMID:18627175 doi:10.1021/bi800212b

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@@ Line 3: / Line 3: @@
 '''Phosphoglycerate dehydrogenase''' (PGDH) catalyzes the conversion of 3-phosphoglycerate into 3-phosphohydroxypyruvate.  This is the first step of serine biosynthesis<ref>PMID:11567059</ref>.  NAD is used as cofactor.
+See also:[[3-Phosphoglycerates: serine, glycine, cysteine]]
 == Relevance ==
@@ Line 8: / Line 10: @@
 == Structural highlights ==
-The active site of ''Mycobacterium tuberculosis'' PGDH located in the cleft between the substrate and the NAD-binding domains contains the <scene name='49/491889/Cv/2'>catalytic dyad Glu:His and the substrate</scene><ref>PMID:18627175</ref>.
+The active site of ''Mycobacterium tuberculosis'' PGDH located in the cleft between the substrate and the NAD-binding domains contains the <scene name='49/491889/Cv/3'>catalytic dyad Glu:His and the substrate</scene><ref>PMID:18627175</ref>.
 See [[Rossmann fold]].
 </StructureSection>
 ==3D structures of phosphoglycerate dehydrogenase==
+Updated on {{REVISIONDAY2}}-{{MONTHNAME|{{REVISIONMONTH}}}}-{{REVISIONYEAR}}
 {{#tree:id=OrganizedByTopic|openlevels=0|
@@ Line 24: / Line 28: @@
 *Phosphoglycerate dehydrogenase binary complex
+**[[2g76]], [[7cvp]] - h3-PGDH + NAD – human<br />
+**[[5n53]], [[5nzo]], [[5nzp]], [[5nzq]], [[5ofv]], [[5ofw]], [[7ewh]] – h3-PGDH + drug<br />
+**[[5ofm]] – h3-PGDH + amino-methyl-indole<br />
+**[[7va1]] – h3-PGDH + thiazole derivative<br />
+**[[7dkm]] – h3-PGDH + inhibitor<br />
 **[[1sc6]], [[2p9c]], [[2p9e]], [[2p9g]] - EcPGDH (mutant) + NAD – ''Escherichia coli''<br />
 **[[1yba]] - EcPGDH + NAD<br />
 **[[1wwk]] - PGDH + NAD – ''Pyrococcus horikoshii''<br />
-**[[2g76]] - h3-PGDH + NAD – human<br />
-**[[5n53]], [[5nzo]], [[5nzp]], [[5nzq]], [[5ofv]], [[5ofw]] – h3-PGDH + drug<br />
-**[[5ofm]] – h3-PGDH + amino-methyl-indole<br />
 **[[2ekl]] - PGDH + NAD – ''Sulfolobus tokodaii''<br />
 **[[3ddn]] - MtPGDH + hydroxypyruvic acid phosphate
@@ Line 35: / Line 41: @@
 *Phosphoglycerate dehydrogenase ternary complex
+**[[5n6c]] – h3-PGDH + NAD + tartrate<br />
+**[[6cwa]] – h3-PGDH + NAD + 3PG<br />
+**[[6plf]], [[6plg]] – h3-PGDH + indole amide derivative<br />
+**[[6rih]], [[6rj2]], [[6rj3]], [[6rj5]], [[6rj6]] – h3-PGDH + inhibitor<br />
 **[[1psd]] - EcPGDH + serine + NAD <br />
 **[[2pa3]] - EcPGDH (mutant) + serine + NAD<br />
-**[[5n6c]] – h3-PGDH + NAD + tartrate<br />
 }}
 == References ==
 <references/>
 [[Category:Topic Page]]