Dihydrofolate+Reductase+(Bacillus+anthracis)

**Gene symbol:** pxo1_110 **Genomic Sequence:** NC_001496.1
 * Target Protein: ** Dihydrofolate Reductase (Bacillus anthracis)
 * E.C. Number: ** 1.5.1.3
 * Gene #: ** 3361714


 * PDB ID: ** 2QK8
 * Protein ID: ** Q81R22
 * Organism: ** Bacillus anthracis


 * Etiological Risk Group: ** Category B Priority Pathogens - //Bacillus anthracis //

Anthrax is a zoonotic disease caused by //Bacillus anthracis//, an aerobic, gram-positive spore-forming bacterium. //Bacillus anthracis// primarily affects herbivores; though most warmed-blooded mammals may be susceptible [[|1]], including humans. Anthrax is an ancient disease that has caused losses of livestock and wildlife populations prior to and throughout the 20th century and remains enzootic with seasonal variations in many parts of the world [[|2], [|3]]. http://journals.plos.org/plosntds/article?id=10.1371/journal.pntd.0004689#abstract0
 * Disease: **

Phagocytes generate nitric oxide (NO) and other reactive oxygen and nitrogen species in large quantities to combat infecting bacteria. Here, we report the surprising observation that in vivo survival of a notorious pathogen—Bacillus anthracis—critically depends on its own NO-synthase (bNOS) activity. Anthrax spores (Sterne strain) deficient in bNOS lose their virulence in an A/J mouse model of systemic infection and exhibit severely compromised survival when germinating within macrophages.
 * Homology: ** Bacillus cereus, Bacillus thuringiensis, and Bacillus mycoides
 * Essentiality: ** Bacillus anthracis-derived nitric oxide is essential for pathogen virulence and survival of macrophages.

@http://www.pnas.org/content/105/3/1009


 * Druggable Target: ** One possible candidate is dihydrofolate reductase (DHFR), a biosynthetic enzyme necessary for anthrax pathogenicity. We determined the crystal structure of DHFR from B. anthracis (baDHFR) in complex with methotrexate.


 * Protein Image: **

Figure 1. PyMol image crystal structure of the anthranx drug target, Bacillus anthracis dihydrofolate reductase

https://www.sigmaaldrich.com/life-science/metabolomics/enzyme-explorer/learning-center/assay-library/ec-number.html
 * Assayable Enzyme Target: **
 * 1.5.1.3 Dihydrofolate Reductase **


 * Structure (PDB or Homology model) **
 * PDB # or closest PDB entry if using homology model: ** 3HMC
 * For Homology Model option: ** N/A
 * Expression System:** Escherichia coli BL21(DE3)
 * Inhibitors:** n/a

https://blast.ncbi.nlm.nih.gov/Blast.cgi#alnHdr_446669140 @http://www.uniprot.org/proteomes/UP000000427 https://www.ncbi.nlm.nih.gov/gene/3361714 >2QK8:A|PDBID|CHAIN|SEQUENCE
 * Pairwise alignment of your BLASTP search in NCBI against the PDB--100% aligned **
 * Gene Availability:**
 * Protein sequence: **

MIVSFMVAMDENRVIGKDNNLPWRLPSELQYVKKTTMGHPLIMGRKNYEAIGRPLPGRRNIIVTRNEGYHVEGCEVAHSV

EEVFELCKNEEEIFIFGGAQIYDLFLPYVDKLYITKIHHAFEGDTFFPEMDMTNWKEVFVEKGLTDEKNPYTYYYHVYEK

QQ
 * length of your protein in Amino Acids: ** 162 aa
 * Molecular Weight of your protein in kiloDaltons using the [|Expasy ProtParam] website: ** 19.124 kDa
 * Molar Extinction coefficient of your protein at 280 nm wavelength: ** 1.439


 * TMpred graph Image ** ( @http://www.ch.embnet.org/software/TMPRED_form.html ).

**CDS Gene Sequence:** code >NC_001496.1:c135455-133161 Bacillus anthracis virulence plasmid PX01, complete sequence ATGAAAAAACGAAAAGTGTTAATACCATTAATGGCATTGTCTACGATATTAGTTTCAAGCACAGGTAATT TAGAGGTGATTCAGGCAGAAGTTAAACAGGAGAACCGGTTATTAAATGAATCAGAATCAAGTTCCCAGGG GTTACTAGGATACTATTTTAGTGATTTGAATTTTCAAGCACCCATGGTGGTTACCTCTTCTACTACAGGG GATTTATCTATTCCTAGTTCTGAGTTAGAAAATATTCCATCGGAAAACCAATATTTTCAATCTGCTATTT GGTCAGGATTTATCAAAGTTAAGAAGAGTGATGAATATACATTTGCTACTTCCGCTGATAATCATGTAAC AATGTGGGTAGATGACCAAGAAGTGATTAATAAAGCTTCTAATTCTAACAAAATCAGATTAGAAAAAGGA AGATTATATCAAATAAAAATTCAATATCAACGAGAAAATCCTACTGAAAAAGGATTGGATTTCAAGTTGT ACTGGACCGATTCTCAAAATAAAAAAGAAGTGATTTCTAGTGATAACTTACAATTGCCAGAATTAAAACA AAAATCTTCGAACTCAAGAAAAAAGCGAAGTACAAGTGCTGGACCTACGGTTCCAGACCGTGACAATGAT GGAATCCCTGATTCATTAGAGGTAGAAGGATATACGGTTGATGTCAAAAATAAAAGAACTTTTCTTTCAC CATGGATTTCTAATATTCATGAAAAGAAAGGATTAACCAAATATAAATCATCTCCTGAAAAATGGAGCAC GGCTTCTGATCCGTACAGTGATTTCGAAAAGGTTACAGGACGGATTGATAAGAATGTATCACCAGAGGCA AGACACCCCCTTGTGGCAGCTTATCCGATTGTACATGTAGATATGGAGAATATTATTCTCTCAAAAAATG AGGATCAATCCACACAGAATACTGATAGTCAAACGAGAACAATAAGTAAAAATACTTCTACAAGTAGGAC ACATACTAGTGAAGTACATGGAAATGCAGAAGTGCATGCGTCGTTCTTTGATATTGGTGGGAGTGTATCT GCAGGATTTAGTAATTCGAATTCAAGTACGGTCGCAATTGATCATTCACTATCTCTAGCAGGGGAAAGAA CTTGGGCTGAAACAATGGGTTTAAATACCGCTGATACAGCAAGATTAAATGCCAATATTAGATATGTAAA TACTGGGACGGCTCCAATCTACAACGTGTTACCAACGACTTCGTTAGTGTTAGGAAAAAATCAAACACTC GCGACAATTAAAGCTAAGGAAAACCAATTAAGTCAAATACTTGCACCTAATAATTATTATCCTTCTAAAA ACTTGGCGCCAATCGCATTAAATGCACAAGACGATTTCAGTTCTACTCCAATTACAATGAATTACAATCA ATTTCTTGAGTTAGAAAAAACGAAACAATTAAGATTAGATACGGATCAAGTATATGGGAATATAGCAACA TACAATTTTGAAAATGGAAGAGTGAGGGTGGATACAGGCTCGAACTGGAGTGAAGTGTTACCGCAAATTC AAGAAACAACTGCACGTATCATTTTTAATGGAAAAGATTTAAATCTGGTAGAAAGGCGGATAGCGGCGGT TAATCCTAGTGATCCATTAGAAACGACTAAACCGGATATGACATTAAAAGAAGCCCTTAAAATAGCATTT GGATTTAACGAACCGAATGGAAACTTACAATATCAAGGGAAAGACATAACCGAATTTGATTTTAATTTCG ATCAACAAACATCTCAAAATATCAAGAATCAGTTAGCGGAATTAAACGCAACTAACATATATACTGTATT AGATAAAATCAAATTAAATGCAAAAATGAATATTTTAATAAGAGATAAACGTTTTCATTATGATAGAAAT AACATAGCAGTTGGGGCGGATGAGTCAGTAGTTAAGGAGGCTCATAGAGAAGTAATTAATTCGTCAACAG AGGGATTATTGTTAAATATTGATAAGGATATAAGAAAAATATTATCAGGTTATATTGTAGAAATTGAAGA TACTGAAGGGCTTAAAGAAGTTATAAATGACAGATATGATATGTTGAATATTTCTAGTTTACGGCAAGAT GGAAAAACATTTATAGATTTTAAAAAATATAATGATAAATTACCGTTATATATAAGTAATCCCAATTATA AGGTAAATGTATATGCTGTTACTAAAGAAAACACTATTATTAATCCTAGTGAGAATGGGGATACTAGTAC CAACGGGATCAAGAAAATTTTAATCTTTTCTAAAAAAGGCTATGAGATAGGATAA

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