3-deoxy-D-glycero-beta-D-galacto-nonulosonate 9-phosphate(3-)

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 3-deoxy-D-glycero-beta-D-galacto-nonulosonate 9-phosphate(3-)
• 英文别名: (2S,4S,5R,6R)-6-[(1R,2R)-1,2-dihydroxy-3-phosphonatooxypropyl]-2,4,5-trihydroxyoxane-2-carboxylate
• 化学式: C9H14O12P-3
• 分子量: 345.17
• InChiKey: KIZXPTJSEKWTPW-YOQZMRDMSA-K

计算性质

• 辛醇/水分配系数(LogP)：
  -4.1
• 重原子数：
  22
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.89
• 拓扑面积：
  223
• 氢给体数：
  5
• 氢受体数：
  12

反应信息

• 作为反应物：
  描述：

  3-deoxy-D-glycero-beta-D-galacto-nonulosonate 9-phosphate(3-) 、 水 生成 3-deoxy-D-glycero-beta-D-galacto-nonulosonate 、 H3PO4
  参考文献：
  名称：

  Human Symbiont Bacteroides thetaiotaomicron Synthesizes 2-Keto-3-Deoxy-D-Glycero-D- Galacto-Nononic Acid (KDN)

  摘要：

  The proper functioning of the human intestine is dependent on its bacterial symbionts, the most predominant of which belong to the Phylum Bacteroidetes. These bacteria are known to use variable displays of multiple capsular polysaccharides (CPs) to aid in their survival and foraging within the intestine. Bacteroides thetaiotaomicron is a prominent human gut symbiont and a remarkably versatile glycophile. The structure determination of the CPs, encoded by the eight CP loci, is the key to understanding the mechanism of this organism's adaptation on a molecular level. Herein, we report the bioinformatics-based discovery and chemical demonstration of a biosynthetic pathway that forms and cytidylates 2-keto-3-deoxy-D-glycero-D-galacto-nononic acid (KDN), most likely for inclusion in the CP encoded by B. thetaiotaomicron CP locus 7.

  DOI：

  10.1016/j.chembiol.2008.08.005
• 作为产物：
  描述：

  mannose 6-phosphate 、 水 、 phosphoenolpyruvate 生成 3-deoxy-D-glycero-beta-D-galacto-nonulosonate 9-phosphate(3-) 、 H3PO4
  参考文献：
  名称：

  KDN（2-酮-3-脱氧-D-甘油-D-半乳糖壬酸）的生物合成。鳟鱼睾丸中KDN-9-磷酸合成酶活性的鉴定和表征。

  摘要：

  尽管脱氨基神经氨酸或KDN糖基（2-酮基-3-脱氧-D-甘油-D-半乳糖-壬酸）在从细菌到人的进化多样性范围内的糖缀合物中表达，但是关于这种新颖的方法的信息很少糖是合成的。因此，在鳟鱼睾丸（一种富含KDN的器官）中开始了生物合成研究，以确定该唾液酸是如何形成的。这些研究表明该途径由以下三个顺序反应组成：1）Man + ATP-> Man-6-P + ADP; 2）Man-6-P + PEP-> KDN-9-P + P（i）; 3）KDN-9-P-> KDN + P（i）。己糖激酶催化的反应1是甘露糖的6-O-磷酸化反应，生成D-甘露糖6-磷酸酯（Man-6-P）。由KDN-9-磷酸（KDN-9-P）合成酶催化的反应2使Man-6-P和磷酸烯醇式丙酮酸（PEP）缩合形成KDN-9-P。反应3，磷酸酶催化的是KDN-9-P的脱磷酸作用，生成游离的KDN。尚不清楚活跃合成KDN的组织中是否可能存

  DOI：

  10.1074/jbc.274.33.22949

文献信息

• Cloning and Expression of the HumanN-Acetylneuraminic Acid Phosphate Synthase Gene with 2-Keto-3-deoxy-d-glycero- d-galacto-nononic Acid Biosynthetic Ability
  作者：Shawn M. Lawrence、Kathleen A. Huddleston、Lee R. Pitts、Nam Nguyen、Yuan C. Lee、Willie F. Vann、Timothy A. Coleman、Michael J. Betenbaugh

  DOI：10.1074/jbc.m000217200

  日期：2000.6

  Sialic acids participate in many important biological recognition events, yet eukaryotic sialic acid biosynthetic genes are not well characterized. In this study, we have identified a novel human gene based on homology to the Escherichia coli sialic acid synthase gene (neuB). The human gene is ubiquitously expressed and encodes a 40-kDa enzyme. The gene partially restores sialic acid synthase activity

  唾液酸参与许多重要的生物学识别事件，但是真核唾液酸生物合成基因尚未很好地表征。在这项研究中，我们已经基于与大肠杆菌唾液酸合酶基因（neuB）的同源性鉴定了一个新的人类基因。人基因普遍表达并编码40 kDa的酶。该基因可在大肠杆菌的neuB阴性突变体中部分恢复唾液酸合酶活性，并产生N-乙酰神经氨酸（Neu5Ac）和2-酮-3-脱氧-D-甘油-D-半乳糖-壬酸（KDN）重组杆状病毒感染后在昆虫细胞中产生杀虫剂。在体外，人类酶使用6-磷酸N-乙酰甘露糖胺和6-磷酸甘露糖作为底物分别生成Neu5Ac和KDN的磷酸化形式，但对Neu5Ac磷酸酯产品表现出高得多的活性。
• Structural Basis for the Divergence of Substrate Specificity and Biological Function within HAD Phosphatases in Lipopolysaccharide and Sialic Acid Biosynthesis
  作者：Kelly D. Daughtry、Hua Huang、Vladimir Malashkevich、Yury Patskovsky、Weifeng Liu、Udupi Ramagopal、J. Michael Sauder、Stephen K. Burley、Steven C. Almo、Debra Dunaway-Mariano、Karen N. Allen

  DOI：10.1021/bi400659k

  日期：2013.8.13

  The haloacid dehalogenase enzyme superfamily (HADSF) is largely composed of phosphatases that have been particularly successful at adaptating to novel biological functions relative to members of other phosphatase families. Herein, we examine the structural basis for the divergence of function in two bacterial homologues: 2-keto-3-deoxy-D-manno-octulosonate 8-phosphate phosphohydrolase (KDO8P phosphatase, KDO8PP) and 2-keto-3-deoxy-9-O-phosphonononic acid phosphohydrolase (KDN9P phosphatase, KDN9PP). KDO8PP and KDN9PP catalyze the final step in KDO and KDN synthesis, respectively, prior to transfer to CMP to form the activated sugar nucleotide. KDO8PP and KDN9PP orthologs derived from an evolutionarily diverse collection of bacterial species were subjected to steady-state kinetic analysis to determine their specificities toward catalyzed KDO8P and ICDN9P hydrolysis. Although each enzyme was more active with its biological substrate, the degree of selectivity (as defined by the ratio of k(cat)/K-m for KDO8P vs KDN9P) varied significantly. High-resolution X-ray structure determination of Haemophilus influenzae KDO8PP bound to KDO/VO3- and Bacteriodes thetaiotaomicron KDN9PP bound to KDN/VO3- revealed the substrate-binding residues. The structures of the KDO8PP and KDN9PP orthologs were also determined to reveal the differences in their active-site structures that underlie the variation in substrate preference. Bioinformatic analysis was carried out to define the sequence divergence among KDN9PP and KDO8PP orthologs. The KDN9PP orthologs were found to exist as single-domain proteins or fused with the pathway nucleotidyl transferases; the fusion of KDO8PP with the transferase is rare. The KDO8PP and KDN9PP orthologs share a stringently conserved Arg residue that forms a salt bridge with the substrate carboxylate group. The split of the KDN9PP lineage from the KDO8PP orthologs is easily tracked by the acquisition of a Glu/Lys pair that supports ICDN9P binding. Moreover, independently evolved lineages of KDO8PP orthologs exist, and are separated by diffuse active-site sequence boundaries. We infer a high tolerance of the KDO8PP catalytic platform to amino acid replacements that in turn influence substrate specificity changes and thereby facilitate the divergence in biological function.
• Structure-Function Analysis of 2-Keto-3-deoxy-D-glycero-D-galactonononate-9-phosphate Phosphatase Defines Specificity Elements in Type C0 Haloalkanoate Dehalogenase Family Members
  作者：Zhibing Lu、Liangbing Wang、Debra Dunaway-Mariano、Karen N. Allen

  DOI：10.1074/jbc.m807056200

  日期：2009.1

  The phosphotransferases of the haloalkanoate dehalogenase superfamily (HADSF) act upon a wide range of metabolites in all eukaryotes and prokaryotes and thus constitute a significant force in cell function. The challenge posed for biochemical function assignment of HADSF members is the identification of the structural determinants that target a specific metabolite. The "8KDOP" subfamily of the HADSF is defined by the known structure and catalytic activity of 2-keto-3-deoxy-8-phospho-d-manno-octulosonic acid (KDO-8-P) phosphatase. Homologues of this enzyme have been uniformly annotated as KDO-8-P phosphatase. One such gene, BT1713, from the Bacteroides thetaiotaomicron genome was recently found to encode the enzyme 2-keto-3-deoxy-d-glycero-d-galacto-9-phosphonononic acid (KDN-9-P) phosphatase in the biosynthetic pathway of the 9-carbon alpha-keto acid, 2-keto-3-deoxy-d-glycero-d-galactonononic acid (KDN). To find the structural elements that provide substrate-specific interactions and to allow identification of genomic sequence markers, the x-ray crystal structures of BT1713 liganded to the cofactor Mg(2+)and complexed with tungstate or VO(3)(-)/Neu5Ac were determined to 1.1, 1.85, and 1.63 A resolution, respectively. The structures define the active site to be at the subunit interface and, as confirmed by steady-state kinetics and site-directed mutagenesis, reveal Arg-64(*), Lys-67(*), and Glu-56 to be the key residues involved in sugar binding that are essential for BT1713 catalytic function. Bioinformatic analyses of the differentially conserved residues between BT1713 and KDO-8-P phosphatase homologues guided by the knowledge of the structure-based specificity determinants define Glu-56 and Lys-67(*) to be the key residues that can be used in future annotations.