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Serine racemase

From Wikipedia, the free encyclopedia
(Redirected from SRR (gene))
SRR
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
AliasesSRR, ILV1, ISO1, serine racemase
External IDsOMIM: 606477; MGI: 1351636; HomoloGene: 22775; GeneCards: SRR; OMA:SRR - orthologs
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_001304803
NM_021947

NM_001163311
NM_013761
NM_001362742
NM_001362743
NM_001362744

RefSeq (protein)

NP_001291732
NP_068766

NP_001156783
NP_038789
NP_001349671
NP_001349672
NP_001349673

Location (UCSC)Chr 17: 2.3 – 2.33 MbChr 11: 74.8 – 74.82 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

Serine racemase (SR, EC 5.1.1.18) is the first racemase enzyme in human biology to be identified. This enzyme converts L-serine to its enantiomer form, D-serine. D-serine acts as a neuronal signaling molecule by activating NMDA receptors in the brain.

Since NMDA receptors Dysfunction has been suggested as one of the promising hypotheses for the pathophysiology of schizophrenia, it has been shown that underexpression of this enzyme is an indicator, especially for the paranoid subtype.[5] Treatment of schizophrenia with D-serine has been shown to play some role in ameliorating some symptoms.[6]

In humans, the serine racemase protein is encoded by the SRR gene.[7] Serine racemase may have evolved from L-thre-hydroxyaspartate (L-THA) eliminase and served as the precursor to aspartate racemase.[8]

Mammalian serine racemase is a pyridoxal 5'-phosphate dependent enzyme that catalyzes both the racemization of L-serine to D-serine and also the elimination of water from L-serine, generating pyruvate and ammonia through the β-elimination of L-serine.[9] This makes serine a known bifurcating enzyme. The β-elimination pathway is thought to serve as a bleed valve that allows local stores of L-serine to be diverted away from D-serine as a means of muting the D-serine signaling pathway. The canonical tetraglycine loop that serves as a PLP phosphate binding pocket includes the active residues being F55, K56, G185, G186, G187, G188, and S313.[8]

PLP in serine racemase

The enzyme is physiologically stimulated by divalent cations (e.g., magnesium) and is allosterically activated by the magnesium/ATP complex, associated with a conformational change upon nucleotide binding that depends upon interactions with Q89. The canonical coordination sphere of the divalent cation interaction site includes the active residues E210 and D216 within 2.1 angstroms of the ion.[8]

Divalent cation (Mn) in serine racemase

References

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  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000167720Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000001323Ensembl, May 2017
  3. ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ^ Morita, Yukitaka; Ujike, Hiroshi; Tanaka, Yuji; Otani, Kyohei; Kishimoto, Makiko; Morio, Akiko; Kotaka, Tatsuya; Okahisa, Yuko; Matsushita, Masayuki; Morikawa, Akiko; Hamase, Kenji (May 2007). "A Genetic Variant of the Serine Racemase Gene Is Associated with Schizophrenia". Biological Psychiatry. 61 (10): 1200–1203. doi:10.1016/j.biopsych.2006.07.025. PMID 17067558. S2CID 8142062.
  6. ^ Fujii, K; Maeda, K; Hikida, T; Mustafa, A K; Balkissoon, R; Xia, J; Yamada, T; Ozeki, Y; Kawahara, R; Okawa, M; Huganir, R L (2006-02-01). "Serine racemase binds to PICK1: potential relevance to schizophrenia". Molecular Psychiatry. 11 (2): 150–157. doi:10.1038/sj.mp.4001776. ISSN 1359-4184. PMID 16314870. S2CID 23387084.
  7. ^ De Miranda J, Santoro A, Engelender S, Wolosker H (Oct 2000). "Human serine racemase: moleular cloning, genomic organization and functional analysis". Gene. 256 (1–2): 183–8. doi:10.1016/S0378-1119(00)00356-5. PMID 11054547.
  8. ^ a b c Graham, Danielle L.; Beio, Matthew L.; Nelson, David L.; Berkowitz, David B. (2019-03-13). "Human Serine Racemase: Key Residues/Active Site Motifs and Their Relation to Enzyme Function". Frontiers in Molecular Biosciences. 6: 8. doi:10.3389/fmolb.2019.00008. ISSN 2296-889X. PMC 6424897. PMID 30918891.
  9. ^ De Miranda J, Panizzutti R, Foltyn VN, Wolosker H (Oct 2002). "Cofactors of serine racemase that physiologically stimulate the synthesis of the N-methyl-D-aspartate (NMDA) receptor coagonist D-serine". Proceedings of the National Academy of Sciences of the United States of America. 99 (22): 14542–7. Bibcode:2002PNAS...9914542D. doi:10.1073/pnas.222421299. PMC 137919. PMID 12393813.

Further reading

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