3fq8 | pdb_00003fq8

M248I mutant of GSAM

spinqualitylabelsall models 3fq8, resolution 2.00Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 3fq8 is a 2 chain structure with sequence from Anacystis nidulans. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: PMP Related: 2hp1, 2hp2, 3fq7, 3fqa Gene: hemL, gsa, syc0881_c (Anacystis nidulans) Activity: Glutamate-1-semialdehyde 2,1-aminomutase, with EC number 5.4.3.8 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMed Gabaculine is a potent inhibitor of the vitamin B6-dependent key enzyme in chlorophyll biosynthesis, glutamate-1-semialdehyde aminomutase (GSAM). The inhibition effect is caused by an enzymatic deprotonation of the neurotoxin and requires the aldimine (PLP) form of the cofactor at the active site. In this study, we show that a single-point mutation confers resistance to gabaculine. A combined functional and structural analysis of wild-type GSAM in complex with gabaculine and the GSAM(M248I) form allowed us to decipher in atomic detail the molecular basis of this unique resistance. Interestingly, the gabaculine tolerance is caused by the absence of an essential water molecule that has a dual functional role. It serves as a nucleophilic shuttle for the hydroxyl anion along the reaction pathway and holds active-site Lys273 in a catalytically competent conformation. The single-point mutant is not able to fix this catalytic water between the beta-branched side chain of Ile248 and Lys273. As a consequence, the mutant enzyme is trapped in a gabaculine-insensitive but still enzymatically active amine (PMP) form. Absence of a catalytic water confers resistance to the neurotoxin gabaculine.,Orriss GL, Patel TR, Sorensen J, Stetefeld J FASEB J. 2010 Feb;24(2):404-14. Epub 2009 Sep 28. PMID:19786580 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Aminomutase 3D structures

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