1x9d

Crystal Structure Of Human Class I alpha-1,2-Mannosidase In Complex With Thio-Disaccharide Substrate Analogue

spinqualitylabelsall models 1x9d, resolution 1.41Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 1x9d 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 1.41Å Ligands: BU1, CA, MAN, SO4, Z5L Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Disease MA1B1_HUMAN Defects in MAN1B1 are the cause of mental retardation autosomal recessive type 15 (MRT15) [MIM:614202. Mental retardation is characterized by significantly below average general intellectual functioning associated with impairments in adaptative behavior and manifested during the developmental period. Function MA1B1_HUMAN Involved in glycoprotein quality control targeting of misfolded glycoproteins for degradation. It primarily trims a single alpha-1,2-linked mannose residue from Man(9)GlcNAc(2) to produce Man(8)GlcNAc(2), but at high enzyme concentrations, as found in the ER quality control compartment (ERQC), it further trims the carbohydrates to Man(5-6)GlcNAc(2). 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 Quality control in the endoplasmic reticulum (ER) determines the fate of newly synthesized glycoproteins toward either correct folding or disposal by ER-associated degradation. Initiation of the disposal process involves selective trimming of N-glycans attached to misfolded glycoproteins by ER alpha-mannosidase I and subsequent recognition by the ER degradation-enhancing alpha-mannosidase-like protein family of lectins, both members of glycosylhydrolase family 47. The unusual inverting hydrolytic mechanism catalyzed by members of this family is investigated here by a combination of kinetic and binding analyses of wild type and mutant forms of human ER alpha-mannosidase I as well as by structural analysis of a co-complex with an uncleaved thiodisaccharide substrate analog. These data reveal the roles of potential catalytic acid and base residues and the identification of a novel (3)S(1) sugar conformation for the bound substrate analog. The co-crystal structure described here, in combination with the (1)C(4) conformation of a previously identified co-complex with the glycone mimic, 1-deoxymannojirimycin, indicates that glycoside bond cleavage proceeds through a least motion conformational twist of a properly predisposed substrate in the -1 subsite. A novel (3)H(4) conformation is proposed as the exploded transition state. Mechanism of class 1 (glycosylhydrolase family 47) {alpha}-mannosidases involved in N-glycan processing and endoplasmic reticulum quality control.,Karaveg K, Siriwardena A, Tempel W, Liu ZJ, Glushka J, Wang BC, Moremen KW J Biol Chem. 2005 Apr 22;280(16):16197-207. Epub 2005 Feb 15. PMID:15713668 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Mannosidase 3D structures

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