Disease relevance of hmp

• We conclude that E. coli produces a soluble haemoglobin-like protein, the product of the hmp gene (for haemoprotein) [1].
• The Mycobacterium tuberculosis hmp gene encodes a protein which is homologous to flavohemoglobin in Escherichia coli [2].

High impact information on hmp

• In aerobic cultures, only 17 genes were significantly up-regulated, including genes known to be involved in NO tolerance, particularly hmp (encoding the NO-consuming flavohemoglobin Hmp) and norV (encoding flavorubredoxin) [3].
• Viability of the hmp mutant in the presence of lethal concentrations of sodium nitroprusside was increased (to 30% survival after 2 h in 5 mM sodium nitroprusside) by overexpressing Vgb or the HD [4].
• The model is supported by the inability of an fnr mutant to generate NO and by the restoration of NO accumulation to hmp mutants upon introducing a plasmid encoding Fnr* (D154A) known to confer activity in the presence of oxygen [5].
• Cellular respiration of the hmp mutant was instantaneously inhibited in the presence of 13.5 microM NO but remained insensitive to NO inhibition when these cells overexpressed Hmp [4].
• To determine the contribution of each domain of Hmp toward NO detoxification, we genetically engineered the Hmp protein and separately expressed the heme (HD) and the flavin (FD) domains in a defined hmp mutant [4].

Chemical compound and disease context of hmp

• A novel mechanism for upregulation of the Escherichia coli K-12 hmp (flavohaemoglobin) gene by the 'NO releaser', S-nitrosoglutathione: nitrosation of homocysteine and modulation of MetR binding to the glyA-hmp intergenic region [6].
• Nitric oxide, nitrite, and Fnr regulation of hmp (flavohemoglobin) gene expression in Escherichia coli K-12 [7].
• The soluble flavohaemoglobin (Hmp) of Escherichia coli, product of the hmp gene, contains haem B and FAD in a single polypeptide of molecular mass 44 kDa [8].

Biological context of hmp

• Isolation and nucleotide sequence of the hmp gene that encodes a haemoglobin-like protein in Escherichia coli K-12 [1].
• As anticipated from up-regulation of hmp expression by nitric oxide (NO), S-nitrosoglutathione (GSNO) or sodium nitroprusside (SNP), the hmp mutant is hypersensitive to these agents [9].
• Although two MetR binding sites are present in this region, only the higher affinity site proximal to hmp is required for hmp induction by GSNO and SNP [6].
• We propose that the previously documented modulation by Hcy of MetR binding to the glyA-hmp intergenic regulatory region regulates hmp transcription [6].
• Induction of hmp by paraquat in the stationary phase was dependent on the global regulator of stationary-phase gene expression, RpoS (sigma S) [10].

Associations of hmp with chemical compounds

• We now show that hmp expression is also upregulated by S-nitrosoglutathione (GSNO, widely used as an NO releaser) and sodium nitroprusside (SNP, which is a NO+ donor) [6].
• As GSNO and SNP upregulate hmp similarly, the NO released in the former case on reaction with homocysteine cannot be involved in hmp regulation [6].
• A monolysogen containing an hmp-lacZ operon fusion was constructed to determine how the hmp promoter is regulated in response to heme ligands (O2, NO) or the presence of anaerobically utilized electron acceptors (nitrate, nitrite) [7].
• Other known superoxide-generating agents (plumbagin, menadione, and phenazine methosulfate) were not effective in inducing hmp expression [10].
• These observations of hmp mRNA induction in response to O2 limitation and nitrosative stress suggest that the hmp gene of M. tuberculosis may have a role in protection of the organism from NO killing under microaerophilic conditions [2].

Other interactions of hmp

• Anaerobic, but not aerobic, expression of phi (hmp-lacZ)1 was stimulated three- to four-fold by an fnr mutation; an apparent Fnr-binding site is present in the hmp promoter [7].
• However, a mutation in rpoS did not prevent an increase in hmp expression by paraquat in exponentially growing cells [10].
• Mutations in oxyR or rob, known regulators of several stress promoters in E. coli, had no effect on the induction of hmp by paraquat [10].
• The hmp promoter is more sensitive to SNP and S-nitroso-N-penicillamine (SNAP) than is the soxS promoter, consistent with the role of Hmp in protection from reactive nitrogen species [9].
• In vivo, sodA-lacZ fusion activity was increased 3-fold by introducing plasmid pPL341, containing the hmp gene, or by growth with paraquat [11].

Analytical, diagnostic and therapeutic context of hmp

• Northern blotting analysis demonstrated that hmp transcription increased when a microaerophilic culture became oxygen limited as it entered stationary phase at 20 days [2].

References