Serine racemase

SRR
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 3L6B, 3L6R
Identifiers
Aliases	SRR, ILV1, ISO1, serine racemase
External IDs	OMIM: 606477; MGI: 1351636; HomoloGene: 22775; GeneCards: SRR; OMA:SRR - orthologs
Gene location (Human) Chr. Chromosome 17 (human) Band 17p13.3 Start 2,303,383 bp End 2,325,260 bp
Gene location (Mouse) Chr. Chromosome 11 (mouse) Band 11|11 B5 Start 74,797,185 bp End 74,816,774 bp
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in ganglionic eminence ventricular zone testicle gonad gastric mucosa muscle of thigh gastrocnemius muscle islet of Langerhans stromal cell of endometrium hair follicle Top expressed in Region I of hippocampus proper right kidney dentate gyrus of hippocampal formation granule cell intercostal muscle primary visual cortex superior frontal gyrus left lobe of liver proximal tubule human kidney ciliary body More reference expression data BioGPS n/a
Gene ontology Molecular function threonine racemase activity nucleotide binding calcium ion binding PDZ domain binding protein homodimerization activity L-serine ammonia-lyase activity isomerase activity glycine binding metal ion binding catalytic activity lyase activity pyridoxal phosphate binding ATP binding magnesium ion binding D-serine ammonia-lyase activity serine racemase activity Cellular component cytoplasm plasma membrane apical part of cell soma cytosol Biological process response to organic cyclic compound serine family amino acid metabolic process L-serine metabolic process cellular amino acid metabolic process D-serine metabolic process ageing pyruvate biosynthetic process response to morphine response to lipopolysaccharide D-serine biosynthetic process metabolism protein homotetramerization brain development L-serine biosynthetic process Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 63826 27364 Ensembl ENSG00000167720 ENSMUSG00000001323 UniProt Q9GZT4 Q9QZX7 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 Mb Chr 11: 74.8 – 74.82 Mb PubMed search
Wikidata
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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. Treatment of schizophrenia with D-serine has been shown to play some role in ameliorating some symptoms.

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

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. 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.

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.

Divalent cation (Mn) in serine racemase

Further reading

• Morita Y, Ujike H, Tanaka Y, Otani K, Kishimoto M, Morio A, Kotaka T, Okahisa Y, Matsushita M, Morikawa A, Hamase K, Zaitsu K, Kuroda S (May 2007). "A genetic variant of the serine racemase gene is associated with schizophrenia". Biological Psychiatry. 61 (10): 1200–3. doi:10.1016/j.biopsych.2006.07.025. PMID 17067558. S2CID 8142062.
• Steffek AE, Haroutunian V, Meador-Woodruff JH (Jul 2006). "Serine racemase protein expression in cortex and hippocampus in schizophrenia". NeuroReport. 17 (11): 1181–5. doi:10.1097/01.wnr.0000230512.01339.72. PMID 16837850. S2CID 35663584.
• Fujii K, Maeda K, Hikida T, Mustafa AK, Balkissoon R, Xia J, Yamada T, Ozeki Y, Kawahara R, Okawa M, Huganir RL, Ujike H, Snyder SH, Sawa A (Feb 2006). "Serine racemase binds to PICK1: potential relevance to schizophrenia". Molecular Psychiatry. 11 (2): 150–7. doi:10.1038/sj.mp.4001776. PMID 16314870. S2CID 23387084.
• Dumin E, Bendikov I, Foltyn VN, Misumi Y, Ikehara Y, Kartvelishvily E, Wolosker H (Jul 2006). "Modulation of D-serine levels via ubiquitin-dependent proteasomal degradation of serine racemase". The Journal of Biological Chemistry. 281 (29): 20291–302. doi:10.1074/jbc.M601971200. PMID 16714286.
• Strísovský K, Jirásková J, Barinka C, Majer P, Rojas C, Slusher BS, Konvalinka J (Jan 2003). "Mouse brain serine racemase catalyzes specific elimination of L-serine to pyruvate". FEBS Letters. 535 (1–3): 44–8. doi:10.1016/s0014-5793(02)03855-3. PMID 12560076. S2CID 43772379.
• Hoffman HE, Jirásková J, Ingr M, Zvelebil M, Konvalinka J (Jan 2009). "Recombinant human serine racemase: enzymologic characterization and comparison with its mouse ortholog". Protein Expression and Purification. 63 (1): 62–7. doi:10.1016/j.pep.2008.09.003. PMID 18812225.
• Sarras H, Semeralul MO, Fadel MP, Feldcamp LA, Labrie V, Wong AH (Jul 2010). "Elevated PICK1 mRNA in schizophrenia increased SRR mRNA in suicide". Schizophrenia Research. 120 (1–3): 236–7. doi:10.1016/j.schres.2010.03.002. PMID 20385472. S2CID 21820692.
• Yamada K, Ohnishi T, Hashimoto K, Ohba H, Iwayama-Shigeno Y, Toyoshima M, Okuno A, Takao H, Toyota T, Minabe Y, Nakamura K, Shimizu E, Itokawa M, Mori N, Iyo M, Yoshikawa T (Jun 2005). "Identification of multiple serine racemase (SRR) mRNA isoforms and genetic analyses of SRR and DAO in schizophrenia and D-serine levels". Biological Psychiatry. 57 (12): 1493–503. doi:10.1016/j.biopsych.2005.03.018. PMID 15953485. S2CID 22811942.
• Xia M, Liu Y, Figueroa DJ, Chiu CS, Wei N, Lawlor AM, Lu P, Sur C, Koblan KS, Connolly TM (Jun 2004). "Characterization and localization of a human serine racemase". Brain Research. Molecular Brain Research. 125 (1–2): 96–104. doi:10.1016/j.molbrainres.2004.03.007. PMID 15193426.

External links

• Serine+racemase at the U.S. National Library of Medicine Medical Subject Headings (MeSH)
• Overview of all the structural information available in the PDB for UniProt: Q9GZT4 (Serine racemase) at the PDBe-KB.