Molecule Information

General Information of the Molecule (ID: Mol00966)

• Name: Flavohemoprotein (HCP) ,Escherichia coli
• Synonyms: Flavohemoglobin; HMP; Hemoglobin-like protein; Nitric oxide dioxygenase; NO oxygenase; NOD; fsrB; hmpA; b2552; JW2536
• Molecule Type: Protein
• Gene Name: hmp
• Gene ID: 66673560
• Sequence:
  MLDAQTIATVKATIPLLVETGPKLTAHFYDRMFTHNPELKEIFNMSNQRNGDQREALFNA
  IAAYASNIENLPALLPAVEKIAQKHTSFQIKPEQYNIVGEHLLATLDEMFSPGQEVLDAW
  GKAYGVLANVFINREAEIYNENASKAGGWEGTRDFRIVAKTPRSALITSFELEPVDGGAV
  AEYRPGQYLGVWLKPEGFPHQEIRQYSLTRKPDGKGYRIAVKREEGGQVSNWLHNHANVG
  DVVKLVAPAGDFFMAVADDTPVTLISAGVGQTPMLAMLDTLAKAGHTAQVNWFHAAENGD
  VHAFADEVKELGQSLPRFTAHTWYRQPSEADRAKGQFDSEGLMDLSKLEGAFSDPTMQFY
  LCGPVGFMQFTAKQLVDLGVKQENIHYECFGPHKVL
• Function: Is involved in NO detoxification in an aerobic process, termed nitric oxide dioxygenase (NOD) reaction that utilizes O(2) and NAD(P)H to convert NO to nitrate, which protects the bacterium from various noxious nitrogen compounds. Therefore, plays a central role in the inducible response to nitrosative stress.; FUNCTION: In the presence of oxygen and NADH, HMP has NADH oxidase activity, which leads to the generation of superoxide and H(2)O(2), both in vitro and in vivo, and it has been suggested that HMP might act as an amplifier of superoxide stress. Under anaerobic conditions, HMP also exhibits nitric oxide reductase and FAD reductase activities. However, all these reactions are much lower than NOD activity.; FUNCTION: Various electron acceptors are also reduced by HMP in vitro, including dihydropterine, ferrisiderophores, ferric citrate, cytochrome c, nitrite, S-nitrosoglutathione, and alkylhydroperoxides. However, it is unknown if these reactions are of any biological significance in vivo.
• Uniprot ID: HMP_ECOLI

Kingdom: N.A.
Phylum: Proteobacteria
Class: Gammaproteobacteria
Order: Enterobacterales
Family: Enterobacteriaceae
Genus: Escherichia
Species: Escherichia coli

Type(s) of Resistant Mechanism of This Molecule

  UAPP: Unusual Activation of Pro-survival Pathway

Drug Resistance Data Categorized by Drug

Approved Drug(s) 1 drug(s) in total

Triclosan

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Disease Class: Escherichia coli infection [1]

• Resistant Disease: Escherichia coli infection [ICD-11: 1A03.0]
• Resistant Drug: Triclosan
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Discovered Using In-vivo Testing Model
• In Vitro Model: E. coli IFN4; 562
• Experiment for Molecule Alteration: Microarray hybridization assay
• Experiment for Drug Resistance: MIC assay
• Mechanism Description: A FabI NAD+ triclosan ternary complex is formed by face-to-face interaction between the phenol ring of triclosan and the nicotinamide ring of NAD+ in the active site of FabI (enoyl-acyl carrier protein reductase) and therefore highly expressed reductases (narGHJI, garR, hcp and yeaA) and dehydrogenases (fdnGHI, ykgEF, garD, gldA and yeiQ) could bind triclosan which were as the NAD(P) cofactor, thus lowering the effective triclosan concentration.

References

• Ref 1: Signature gene expression profile of triclosan-resistant Escherichia coli. J Antimicrob Chemother. 2010 Jun;65(6):1171-7. doi: 10.1093/jac/dkq114. Epub 2010 Apr 21.