4h27

Modulating the function of human serine racemase and human serine dehydratase by protein engineering

spinqualitylabelsall models 4h27, resolution 1.30Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4h27 is a 1 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.3Å Ligands: LLP, SO4 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function SDHL_HUMAN Publication Abstract from PubMed d-Serine is a co-agonist of N-methyl d-aspartate, a glutamate receptor, which is a major excitatory neurotransmitter receptor in the brain. Human serine racemase (hSR) and serine dehydratase (hSDH) are two important pyridoxal-5'-phosphate-dependent enzymes that synthesize and degrade d-serine, respectively. hSR and hSDH have significant sequence homology (28% identity) and are similar in their structural folds (root-mean-square deviation, 1.12 A). Sequence alignment and structural comparison between hSR and hSDH reveal that S84 in hSR and A65 in hSDH play important roles in their respective enzyme activities. We surmise that exchange of these two amino acids by introducing S84A hSR and A65S hSDH mutants may result in switching their protein functions. To understand the modulating mechanism of the key residues, mutants S84A in hSR and A65S in hSDH were constructed to monitor the change of activities. The structure of A65S hSDH mutant was determined at 1.3 A resolution (PDB 4H27), elucidating the role of this critical amino acid. Our study demonstrated S84A hSR mutant behaved like hSDH, whereas A65S hSDH mutant acquired an additional function of using d-serine as a substrate. Modulating the function of human serine racemase and human serine dehydratase by protein engineering.,Wang CY, Ku SC, Lee CC, Wang AH Protein Eng Des Sel. 2012 Nov;25(11):741-9. doi: 10.1093/protein/gzs078. Epub, 2012 Oct 30. PMID:23112234 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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