Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:O75191 (H. influenzae)
 4,961 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Copper-zinc superoxide dismutases ([Cu,Zn]-SODs) are ubiquitous in eukaryotes but have rarely been found in prokaryotes. A gene for [Cu,Zn]-SOD (sodC) has recently been cloned from Haemophilus influenzae type b and H. parainfluenzae, so other Haemophilus and related species were screened for the presence of [Cu,Zn]-SODs by visualization of bands of SOD activity in non-denaturing polyacrylamide gels and by gene probing. Strains of H. aphrophilus, H. paraphrophilus, H. haemolyticus, H. paraphrohaemolyticus, some non-typable H. influenzae, H. haemoglobinophilus (canis) and H. parasuis were all found to have [Cu,Zn]-SOD activity (inhibited by 2 mM-cyanide) in polyacrylamide gels. In a Southern blot analysis, DNA from H. aphrophilus, H. paraphrophilus, H. haemolyticus and [Cu,Zn]-SOD-containing non-typable H. influenzae--but not the other species--hybridized to a 360 nucleotide DNA probe containing the 5'-part of sodC cloned from H. influenzae type b. Bacterial [Cu,Zn]-SODs are more prevalent than has previously been recognized.
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PMID:Copper-zinc superoxide dismutase in Haemophilus species. 159 63

Copper-zinc superoxide dismutase ([Cu,Zn]-SOD) is widely found in eukaryotes but has only rarely been identified in bacteria. Here we describe sodC, encoding [Cu,Zn]-SOD in Haemophilus influenzae and H. parainfluenzae, frequent colonists and pathogens of the human respiratory tract. In capsulate H. influenzae, sodC was found in only one division of the bacterial population, and although the protein it encoded was clearly [Cu,Zn]-SOD from its deduced sequence, it lacked enzymatic activity. In H. parainfluenzae, in contrast, active enzyme was synthesized which appeared to be secreted beyond the cytoplasm when the gene was expressed in Escherichia coli minicells. The origin of gene transcription differed between the Haemophilus species, but protein synthesis from cloned genes in vitro was comparable. A C-T transition was found in the H. influenzae sequence compared with the H. parainfluenzae sequence, leading to a histidine, known to be crucial in eukaryotic [Cu,Zn]-SOD for copper ion coordination and so for enzymatic activity, to be changed to tyrosine. This is speculated to be the cause of inactivity of the H. influenzae enzyme. Secreted SODs have only been described in a few bacterial species, and this is the first identification of [Cu,Zn]-SOD in a common human upper respiratory tract colonist. The role of secreted bacterial SODs is unknown, and we speculate that in Haemophilus species the enzyme may confer survival advantage by accelerating dismutation of superoxide of environmental origin to hydrogen peroxide, disruptive to the normal mucociliary clearance process in the host.
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PMID:Copper-zinc superoxide dismutase of Haemophilus influenzae and H. parainfluenzae. 193 42

Oxygen free radicals present a serious potential threat to microbial survival, through their ability to inflict indiscriminate damage on proteins and DNA. Superoxide dismutase (SOD, EC 1.15.1.1), among other oxygen-metabolizing enzymes, is essential to prevent these toxic molecules from accumulating in the bacterial cytosol during aerobic metabolism. The gene sodA, encoding manganese-containing SOD ([Mn]-SOD), has been cloned from a virulent strain of Haemophilus influenzae type b using degenerate oligonucleotides encoding regions of the gene conserved across different bacterial species. The gene product has been identified as [MN]-SOD by its similarity at key amino acid residues to known examples of the enzyme, by expression of enzymatically active protein from cloned DNA expressed in Escherichia coli, and by demonstration that an in-frame deletion in the gene abolishes this activity. In contrast to the situation in E. coli, this [Mn]-SOD is the only active SOD detected in H. influenzae. In further contrast to E. coli, [Mn]-SOD gene expression in H. influenzae has been found to be only partially repressed under anaerobic conditions. When expressed in E. coli the gene is regulated by Fur and Fnr, and the promoter region, identified experimentally, has been found to contain nucleotide sequence motifs similar to the Fur- and Fnr-binding sequences of E. coli, suggesting the involvement of analogues of these aerobiosis-responsive activators in H. influenzae gene expression.
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PMID:Molecular and genetic characterization of superoxide dismutase in Haemophilus influenzae type b. 793 46

An enzyme having the same L-cysteine desulfurization activity previously described for the NifS protein was purified from a strain of Azotobacter vinelandii deleted for the nifS gene. This protein was designated IscS to indicate its proposed role in iron-sulfur cluster assembly. Like NifS, IscS is a pyridoxal-phosphate containing homodimer. Information gained from microsequencing of oligopeptides obtained by tryptic digestion of purified IscS was used to design a strategy for isolation and DNA sequence analysis of a 7,886-base pair A. vinelandii genomic segment that includes the iscS gene. The iscS gene is contained within a gene cluster that includes homologs to nifU and another gene contained within the major nif cluster of A. vinelandii previously designated orf6. These genes have been designated iscU and iscA, respectively. Information available from complete genome sequences of Escherichia coli and Hemophilus influenzae reveals that they also encode iscSUA gene clusters. A wide conservation of iscSUA genes in nature and evidence that NifU and NifS participate in the mobilization of iron and sulfur for nitrogenase-specific iron-sulfur cluster formation suggest that the products of the iscSUA genes could play a general role in the formation or repair of iron-sulfur clusters. The proposal that IscS is involved in mobilization of sulfur for iron-sulfur cluster formation in A. vinelandii is supported by the presence of a cysE-like homolog in another gene cluster located immediately upstream from the one containing the iscSUA genes. O-Acetylserine synthase is the product of the cysE gene, and it catalyzes the rate-limiting step in cysteine biosynthesis. A similar cysE-like gene is also located within the nif gene cluster of A. vinelandii. The likely role of such cysE-like gene products is to increase the cysteine pool needed for iron-sulfur cluster formation. Another feature of the iscSUA gene cluster region from A. vinelandii is that E. coli genes previously designated as hscB, hscA, and fdx are located immediately downstream from, and are probably co-transcribed with, the iscSUA genes. The hscB, hscA, and fdx genes are also located adjacent to the iscSUA genes in both E. coli and H. influenzae. The E. coli hscA and hscB gene products have previously been shown to bear primary sequence identity when respectively compared with the dnaK and dnaJ gene products and have been proposed to be members of a heat-shock-cognate molecular chaperone system of unknown function. The close proximity and apparent co-expression of iscSUA and hscBA in A. vinelandii indicate that the proposed chaperone function of the hscBA gene products could be related to the maturation of iron-sulfur cluster-containing proteins. Attempts to place non-polar insertion mutations within either A. vinelandii iscS or hscA revealed that such mutations could not be stably maintained in the absence of the corresponding wild-type allele. These results reveal a very strong selective pressure against the maintenance of A. vinelandii iscS or hscA knock-out mutations and suggest that such mutations are either lethal or highly deleterious. In contrast to iscS or hscA, a strain having a polar insertion mutation within the cysE-like gene was readily isolated and could be stably maintained. These results show that the cysE-like gene located upstream from iscS is not essential for cell growth and that the cysE-like gene and the iscSUA-hscBA-fdx genes are contained within separate transcription units.
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PMID:Assembly of iron-sulfur clusters. Identification of an iscSUA-hscBA-fdx gene cluster from Azotobacter vinelandii. 958 71

Substrate selection by AAA+ ATPases that function to unfold proteins or alter protein conformation is often regulated by delivery or adaptor proteins. SspB is a protein dimer that binds to the ssrA degradation tag and delivers proteins bearing this tag to ClpXP, an AAA+ protease, for degradation. Here, we describe the structure of the peptide binding domain of H. influenzae SspB in complex with an ssrA peptide at 1.6 A resolution. The ssrA peptides are bound in well-defined clefts located at the extreme ends of the SspB homodimer. SspB contacts residues within the N-terminal and central regions of the 11 residue ssrA tag but leaves the C-terminal residues exposed and positioned to dock with ClpX. This structure, taken together with biochemical analysis of SspB, suggests mechanisms by which proteins like SspB escort substrates to AAA+ ATPases and enhance the specificity and affinity of target recognition.
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PMID:Structure of a delivery protein for an AAA+ protease in complex with a peptide degradation tag. 1453 76

The cDNA sequence of the gene for xylose isomerase from the rumen fungus Orpinomyces was elucidated by rapid amplification of cDNA ends. The 1,314-nucleotide gene was cloned and expressed constitutively in Saccharomyces cerevisiae. The deduced polypeptide sequence encoded a protein of 437 amino acids which showed the highest similarity to the family II xylose isomerases. Further, characterization revealed that the recombinant enzyme was a homodimer with a subunit of molecular mass 49 kDa. Cell extract of the recombinant strain exhibited high specific xylose isomerase activity. The pH optimum of the enzyme was 7.5, while the low temperature optimum at 37 degrees C was the property that differed significantly from the majority of the reported thermophilic xylose isomerases. In addition to the xylose isomerase gene, the overexpression of the S. cerevisiae endogenous xylulokinase gene and the Pichia stipitis SUT1 gene for sugar transporter in the recombinant yeast facilitated the efficient production of ethanol from xylose.
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PMID:Xylose isomerase from polycentric fungus Orpinomyces: gene sequencing, cloning, and expression in Saccharomyces cerevisiae for bioconversion of xylose to ethanol. 1905 Aug 60

Bacterial type II toxin-antitoxin (TA) modules encode a toxic protein that downregulates metabolism and a specific antitoxin that binds and inhibits the toxin during normal growth. In non-typeable Haemophilus influenzae, a common cause of infections in humans, the vapXD locus was found to constitute a functional TA module and contribute to pathogenicity; however, the mode of action of VapD and the mechanism of inhibition by the VapX antitoxin remain unknown. Here, we report the structure of the intact H. influenzae VapXD complex, revealing an unusual 2:1 TA molecular stoichiometry where a Cas2-like homodimer of VapD binds a single VapX antitoxin. VapX consists of an oligonucleotide/oligosaccharide-binding domain that docks into an asymmetrical cavity on the toxin dimer. Structures of isolated VapD further reveal how a symmetrical toxin homodimer adapts to interacting with an asymmetrical antitoxin and suggest how a primordial TA system evolved to become part of CRISPR-Cas immunity systems.
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PMID:Structural Basis for Toxin Inhibition in the VapXD Toxin-Antitoxin System. 3309 14