Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0348321 (Haemophilus)
 15,372 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A 3.9 kb Haemophilus influenzae genomic DNA fragment was cloned in plasmid pUC9 that partially complemented the ultraviolet light sensitivity (UVs) of Escherichia coli uvrC mutant hosts. This fragment also complemented the UVs of H. influenzae uvr-1 (DB112) and uvr-2 (DB116) mutants. It genetically transformed the latter mutants to wild type UV resistance. The nucleotide (nt) sequence of this fragment revealed 3 open reading frames (ORFs). ORF2, now designated uvr-1+ (1746 nt), shows significant similarity in both the nt and amino acid (aa) composition to 7 complete proven or putative uvrC gene sequences. Computer analysis of the DNA sequence revealed several possible regulatory motifs 5' to uvr-1+, including a putative LexA-binding site as an inverted SOS box, located within the 3' region of ORF1, (extensive homology to the E. coli CMP-KDO synthetase gene), upstream of uvr-1+. Further computer analysis has also predicted that the four putative active site amino acids, located in the C-terminal half of each protein, are each situated in an area of secondary structure that are highly conserved.
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PMID:Structure of the Haemophilus influenzae uvr-1+ gene: homology with other uvrC-like genes and characterization of the Haemophilus influenzae uvr-1 and uvr-2 mutations. 927 62

The enzyme 3-deoxy-manno-octulosonate cytidylyltransferase (CMP-KDO synthetase; CKS) catalyzes the activation of 3-deoxy-manno-octulosonate (KDO) by forming CMP-KDO. It is essential for the biosynthesis of lipopolysaccharides in Gram-negative bacteria and is a potential target for the discovery of antibacterial agents. L-CKS from Haemophilus influenzae was overexpressed with a C-terminal hexahistidine tag in Escherichia coli and crystallized in the presence of the substrate KDO at 297 K using PEG 4000 as a precipitant and ethylene glycol as an additive. The diffraction limit and spot shape of the native crystal could be improved significantly by dehydration/annealing. X-ray diffraction data were collected to 2.5 A resolution from a native crystal. The crystals are orthorhombic, belonging to the space group P2(1)2(1)2(1), with unit-cell parameters a = 48.6, b = 83.1, c = 117.3 A. The presence of two monomers of recombinant L-CKS in the crystallographic asymmetric unit gives a reasonable V(M) of 2.05 A(3) Da(-1), with a solvent content of 40.0%.
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PMID:Crystallization and preliminary X-ray crystallographic studies of 3-deoxy-manno-octulosonate cytidylyltransferase from Haemophilus influenzae. 1249 64

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.
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PMID:Structure of 3-deoxy-manno-octulosonate cytidylyltransferase from Haemophilus influenzae complexed with the substrate 3-deoxy-manno-octulosonate in the beta-configuration. 1901 7