6b9p

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Structure of GH 38 Jack Bean alpha-mannosidase in complex with a 36-valent iminosugar cluster inhibitorStructure of GH 38 Jack Bean alpha-mannosidase in complex with a 36-valent iminosugar cluster inhibitor

Structural highlights

6b9p is a 2 chain structure with sequence from Canavalia ensiformis. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 1.996Å
Ligands:, , , ,
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

MANA_CANEN Liberates mannose from p-nitrophenyl-alpha-D-mannoside (PubMed:1156387, PubMed:12325362, PubMed:4973951). Liberates mannose from further alpha-D-mannosides including methyl-, benzyl-alpha-D-mannoside, 1-6-linked di-, tri- and tetrasaccharides of alpha-D-mannose and mannosyl-rhamnose (PubMed:12325362). Liberates mannose from various glycoproteins like ovalbumin and ovomucoid (PubMed:12325362, PubMed:5145). Does not hydrolyze beta-D-mannosides (PubMed:12325362). Has glycosyltransferase activity, forming disaccharides from mannose and lyxose but not from glucose, galactose, ribose, xylose or arabinose (PubMed:12325362).[1] [2] [3] [4]

Publication Abstract from PubMed

Multivalent design of glycosidase inhibitors is a promising strategy for the treatment of diseases involving enzymatic hydrolysis of glycosidic bonds in carbohydrates. An essential prerequisite for successful applications is the atomic-level understanding of how outstanding binding enhancement occurs with multivalent inhibitors. Herein we report the first high-resolution crystal structures of the Jack bean alpha-mannosidase (JBalpha-man) in apo and inhibited states. The three-dimensional structure of JBalpha-man in complex with the multimeric cyclopeptoid-based inhibitor displaying the largest binding enhancements reported so far provides decisive insight into the molecular mechanisms underlying multivalent effects in glycosidase inhibition.

Structural Basis of Outstanding Multivalent Effects in Jack Bean alpha-Mannosidase Inhibition.,Howard E, Cousido-Siah A, Lepage ML, Schneider JP, Bodlenner A, Mitschler A, Meli A, Izzo I, Alvarez HA, Podjarny A, Compain P Angew Chem Int Ed Engl. 2018 Jul 2;57(27):8002-8006. doi: 10.1002/anie.201801202., Epub 2018 Jun 6. PMID:29722924[5]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

See Also

References

  1. ↑ Snaith SM. Characterization of jack-bean alpha-D-mannosidase as a zinc metalloenzyme. Biochem J. 1975 Apr;147(1):83-90. PMID:1156387 doi:10.1042/bj1470083
  2. ↑ Li YT. Studies on the glycosidases in jack bean meal. I. Isolation and properties of alpha-mannosidase. J Biol Chem. 1967 Dec 10;242(23):5474-80 PMID:12325362
  3. ↑ Snaith SM, Levvy GA. Purification and properties of alpha-D-mannosidase from jack-bean meal. Biochem J. 1968 Dec;110(4):663-70. PMID:4973951 doi:10.1042/bj1100663
  4. ↑ Sheperd V, Montgomery R. Alpha-D-Mannosidase. Preparation and properties of free and insolubilized enzyme. Biochim Biophys Acta. 1976 May 13;429(3):884-94. PMID:5145 doi:10.1016/0005-2744(76)90334-x
  5. ↑ Howard E, Cousido-Siah A, Lepage ML, Schneider JP, Bodlenner A, Mitschler A, Meli A, Izzo I, Alvarez HA, Podjarny A, Compain P. Structural Basis of Outstanding Multivalent Effects in Jack Bean alpha-Mannosidase Inhibition. Angew Chem Int Ed Engl. 2018 Jul 2;57(27):8002-8006. doi: 10.1002/anie.201801202., Epub 2018 Jun 6. PMID:29722924 doi:http://dx.doi.org/10.1002/anie.201801202

6b9p, resolution 2.00Å

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