title: Structure of 3-deoxy-manno-octulosonate cytidylyltransferase from Haemophilus influenzae complexed with the substrate 3-deoxy-manno-octulosonate in the beta-configuration.
abstract: The enzyme 3-deoxy-manno-octulosonate cytidylyltransferase (CMP-KDO synthetase; CKS) catalyzes the activation of 3-deoxy-D-manno-octulosonate (or 2-keto-3-deoxy-manno-octonic acid; KDO) by forming CMP-KDO. CKS is unique to Gram-negative bacteria and is an attractive target for the development of antibacterial agents. The crystal structure of CKS from Haemophilus influenzae in complex with the substrate KDO has been determined at 2.30 A resolution by combining single-wavelength anomalous diffraction and molecular-replacement methods. The two monomers in the asymmetric unit differ in the conformation of their C-terminal alpha-helix (Ala230-Asn254). The KDO bound to the active site exists as the beta-pyranose form in the (5)C(2) chair conformation. The structure of CKS from H. influenzae in complex with KDO will be useful in structure-based inhibitor design.
authors.affiliation: Department of Chemistry, College of Natural Sciences, Seoul National University, Seoul 151-747, Republic of Korea.
authors.forename: Hye-Jin
authors.initials: HJ
authors.lastname: Yoon
authors.forename: Min-Je
authors.initials: MJ
authors.lastname: Ku
authors.forename: Bunzo
authors.initials: B
authors.lastname: Mikami
authors.forename: Se Won
authors.initials: SW
authors.lastname: Suh
mesh_terms: D000900:Anti-Bacterial Agents / Q000737:chemistry* / Q000378:metabolism / Q000627:therapeutic use; D003460:Crystallization; D015195:Drug Design; D006090:Gram-Negative Bacteria / Q000201:enzymology*; D016905:Gram-Negative Bacterial Infections / Q000628:therapy; D006193:Haemophilus influenzae; D006801:Humans; D009713:Nucleotidyltransferases / Q000737:chemistry* / Q000378:metabolism / Q000627:therapeutic use; D011485:Protein Binding; D017433:Protein Structure, Secondary; D013329:Structure-Activity Relationship; D013379:Substrate Specificity; D013400:Sugar Acids / Q000737:chemistry / Q000378:metabolism*
chemical_list: D000900:Anti-Bacterial Agents; D013400:Sugar Acids; C002532:2-keto-3-deoxyoctonate; D009713:Nucleotidyltransferases; C028984:3-deoxy-manno-octulosonate cytidyltransferase