View source for 6lhm


==Structure of human PYCR2==
<StructureSection load='6lhm' size='340' side='right'caption='[[6lhm]], [[Resolution|resolution]] 3.40&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6lhm]] is a 5 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6LHM OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6LHM FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 3.4&#8491;</td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=6lhm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6lhm OCA], [https://pdbe.org/6lhm PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6lhm RCSB], [https://www.ebi.ac.uk/pdbsum/6lhm PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6lhm ProSAT]</span></td></tr>
</table>
== Disease ==
[https://www.uniprot.org/uniprot/P5CR2_HUMAN P5CR2_HUMAN] PYCR2-related microcephaly-progressive leukoencephalopathy;Autosomal recessive primary microcephaly. The disease is caused by variants affecting the gene represented in this entry.
== Function ==
[https://www.uniprot.org/uniprot/P5CR2_HUMAN P5CR2_HUMAN] Housekeeping enzyme that catalyzes the last step in proline biosynthesis. In some cell types, such as erythrocytes, its primary function may be the generation of NADP(+). Can utilize both NAD and NADP. Has higher affinity for NADP, but higher catalytic efficiency with NADH (PubMed:2722838, PubMed:6894153). Involved in cellular response to oxidative stress (PubMed:25865492).<ref>PMID:25865492</ref> <ref>PMID:2722838</ref> <ref>PMID:6894153</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Patients lacking PYCR2, a mitochondrial enzyme that synthesizes proline, display postnatal degenerative microcephaly with hypomyelination. Here we report the crystal structure of the PYCR2 apo-enzyme and show that a novel germline p.Gly249Val mutation lies at the dimer interface and lowers its enzymatic activity. We find that knocking out Pycr2 in mice phenocopies the human disorder and depletes PYCR1 levels in neural lineages. In situ quantification of neurotransmitters in the brains of PYCR2 mutant mice and patients revealed a signature of encephalopathy driven by excessive cerebral glycine. Mechanistically, we demonstrate that loss of PYCR2 upregulates SHMT2, which is responsible for glycine synthesis. This hyperglycemia could be partially reversed by SHMT2 knockdown, which rescued the axonal beading and neurite lengths of cultured Pycr2 knockout neurons. Our findings identify the glycine metabolic pathway as a possible intervention point to alleviate the neurological symptoms of PYCR2-mutant patients.

Loss of PYCR2 Causes Neurodegeneration by Increasing Cerebral Glycine Levels via SHMT2.,Escande-Beillard N, Loh A, Saleem SN, Kanata K, Hashimoto Y, Altunoglu U, Metoska A, Grandjean J, Ng FM, Pomp O, Baburajendran N, Wong J, Hill J, Beillard E, Cozzone P, Zaki M, Kayserili H, Hamada H, Shiratori H, Reversade B Neuron. 2020 Jul 8;107(1):82-94.e6. doi: 10.1016/j.neuron.2020.03.028. Epub 2020 , Apr 23. PMID:32330411<ref>PMID:32330411</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 6lhm" style="background-color:#fffaf0;"></div>

==See Also==
*[[Pyrroline-5-carboxylate reductase|Pyrroline-5-carboxylate reductase]]
== References ==
<references/>
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Baburajendran N]]