Target-+succinate+dehydrogenase+(Plasmodium+falciparum)

Symbol: PF10_0334 Gene ID: 810491 [|PlasmoDB / PF10_0334] [|GeneDB / PF10_0334]
 * 5, (1)*Target (protein/gene name):** succinate dehydrogenase
 * NCBI Gene # or RefSeq#:**
 * Protein ID (NP or XP #) or Wolbachia#:**
 * Organism (including strain):** Plasmodium falciparum
 * Etiologic Risk Group (see link below):** Appendix B-II-C. Risk Group 2 (RG2) - Parasitic Agents
 * Background/Disease Information (sort of like the Intro to your Mini Research Write up):**

//Plasmodium falciparum// is a parasite that is one of the most common causes of malaria. In 2002, it was estimated that 2.2 billion people were exposed to malaria, resulting in approximately 515 million clinical attacks of this disease. The majority (~70%) of incidence of this disease in 2002 occurred in Africa, with a substantial incidence rate (~25%) in Southeast Asia [1]. A global map depicting the endemicity of malaria in 2007 showed high endemicity in Africa, low endemicity with pockets of mid to high endemicity in Central/Southeast Asia, and uniformly low endemicity in the Americas [2].

Because malaria is generally concentrated in lower income countries, the ideal treatment option for malaria would be cheap, single-dose and have minimal side effects. However, the current treatment options fall short of meeting this criteria. For decades, choroquine (CQ) was the main treatment option for malaria; however, as years passed, CQ-resistant malaria developed. Today, CQ is no longer a viable treatment option for most instances of malaria. Other drugs used in malaria treatment have serious side effects. As such, there is a pronounced need for novel anti-malarial drugs [3].

This protein is essential because according to the journal article regarding purification of the protein, the SDH enzyme would be a good drug target for antimalarial drugs.
 * Essentiality of this protein:**
 * Complex of proteins?:** no
 * Druggable Target:**​ Yes-druggability is 1

1.3.99.1 http://www.brenda-enzymes.org/php/result_flat.php4?ecno=1.3.99.1
 * *EC#: **
 * Link to BRENDA EC# page:**

spectrophotometric http://www.sciencedirect.com/science/article/pii/S0166685199001802
 * --** Show screenshot of BRENDA enzyme mechanism schematic
 * Enzyme Assay information (spectrophotometric, coupled assay ?, reagents):**
 * -- link to Sigma (or other company) page for assay or assay reagents (substrates):** no information available on Sigma
 * -- link (or citation) to paper that contains assay information**

http://www.sciencedirect.com/science/article/pii/S0005272813000893 (E. coli) http://www.sigmaaldrich.com/catalog/product/sigma/p9625?lang=en&region=US
 * -- List cost and quantity of substrate reagents and supplier:**

-- PDB # or closest PDB entry if using homology model: -- For Homology Model option: Show pairwise alignment of your BLASTP search in NCBI against the PDB Query Coverage: 97% Max % Identities: 62% % Positives: 74% Chain used for homology: Chain A, crystal structure of mitochondrial respiratory complex li from porcine heart at 2.4 Angstroms
 * Structure Available (PDB or Homology model)**

Inhibitors for the protein have not been tested in P. falciparum, but in E. coli, there are 11 known inhibitors for succinate dehydrogenase. http://www.ncbi.nlm.nih.gov/pubmed/15847182 SDH has been expressed in E.coli. http://www.sciencedirect.com/science/article/pii/S0166685199001802 Fast protein liquid chromatographic system MIRNNKKYIRFMQSSFCRFSNIKTKAYDIIDHHYDAVIVGAGGAGLRSALELSKNKYKVA CISKLFPTRSHTVAAQGGINAALGNMTEDDWRWHAYDTIKGSDWLGDQNAIHYMCREAPD SVLELEEFGLPFSRTKDGKIYQRAFGGQSLKYGKGGQAYRCAAAADRTGHAMLHTLYGQS LSYNCIFFVEYFVLDLLMLNSNECIGVICINIADGKIHRFFTPHTVIATGGYGRAYLSCT SAHACTGDGNAIVARSKLPLQDLEFVQFHPTGIYPAGCLITEGCRGEGGILRNKEGEAFM MRYAPKAKDLASRDVVSRAMTIEINEQRGCGPNADHIYLDLTHLPYETLKERLPGIMETA KIFAGVDVTKQYIPVLPTVHYNMGGIPTNYKTQVLTQNVNFNKQTNKSNEDIIVKGLYAA GEAASASVHGANRLGANSLLDIVVFGKRAALTIMEIDKPNIPKINANTNIGEESIQRLDH IRFNKGSIQTSQLRKKMQICMQKHAAVFRIGPLLQEGYKQILEICSIFKDIEITDKTLTW NTDLLETLELENLLTLASQTILAAVERKESRGAHARDDFPERDDKNYLKHSLTWMTDRNI ENTKYFTTYRDVITKPLDNEMEYVPPVKRV 70694.8 kDa Extinction coefficients are in units of M-1 cm-1, at 280 nm measured in water. Ext. coefficient 70095 Abs 0.1% (=1 g/l) 0.992, assuming all pairs of Cys residues form cystines Ext. coefficient 69220 Abs 0.1% (=1 g/l) 0.979, assuming all Cys residues are reduced
 * Current Inhibitors:**
 * Expression Information (has it been expressed in bacterial cells)**
 * Purification Method:**
 * Image of protein (PyMol with features delineated and shown separately):**
 * Amino Acid Sequence (paste as text only - not as screenshot or as 'code'):**
 * length of your protein in Amino Acids** 631 amino acids
 * Molecular Weight of your protein in kiloDaltons using the [|Expasy ProtParam]website**
 * Molar Extinction coefficient of your protein at 280 nm wavelength:**


 * TMpred graph Image ** (@http://www.ch.embnet.org/software/TMPRED_form.html). Input your amino acid sequence to it.

ATGATTAGGAATAATAAAAAATACATAAGATTTATGCAATCAAGTTTTTGTAGATTCTCAAATATTAAAA CGAAAGCATATGATATAATTGATCATCATTATGATGCAGTAATTGTAGGAGCTGGAGGTGCTGGATTAAG ATCTGCATTGGAATTATCAAAAAATAAATACAAGGTAGCATGTATCAGTAAATTGTTTCCAACACGATCA CATACTGTAGCTGCTCAAGGTGGAATAAATGCAGCTTTAGGTAATATGACTGAAGATGATTGGAGATGGC ATGCTTATGATACTATCAAAGGTTCAGATTGGCTTGGGGATCAAAACGCTATTCATTATATGTGTAGAGA AGCTCCTGATTCTGTATTAGAATTAGAAGAATTTGGACTCCCGTTTTCAAGAACAAAAGATGGGAAAATA TATCAAAGAGCTTTTGGAGGACAAAGTTTAAAATATGGTAAAGGAGGACAAGCTTATAGATGTGCTGCCG CTGCTGATAGAACAGGACATGCCATGTTACATACATTATATGGACAATCCTTATCTTACAATTGTATATT TTTTGTAGAATATTTTGTTTTAGATTTACTTATGTTAAATTCTAATGAATGTATTGGGGTAATCTGTATT AATATAGCAGATGGAAAAATACATAGATTTTTTACACCACATACTGTTATAGCTACTGGGGGATATGGTC GAGCTTATTTGTCTTGTACATCTGCTCATGCATGTACAGGAGATGGTAATGCCATTGTAGCTAGAAGTAA ATTACCATTACAAGATTTAGAATTTGTACAATTTCATCCAACAGGTATATACCCAGCTGGATGCTTAATT ACTGAAGGATGTAGAGGAGAAGGTGGTATTTTAAGAAATAAAGAAGGAGAAGCCTTTATGATGAGATATG CACCTAAAGCAAAAGATTTAGCTAGTCGTGATGTTGTTAGTAGAGCTATGACCATAGAAATTAATGAACA AAGAGGATGTGGACCAAACGCAGATCATATATATTTAGATTTAACACATTTACCATATGAAACATTAAAA GAAAGATTACCAGGCATAATGGAAACTGCAAAAATTTTTGCGGGAGTTGATGTAACTAAACAATATATTC CTGTCTTACCAACAGTTCATTATAATATGGGTGGAATTCCAACTAATTATAAAACACAAGTGTTAACACA AAACGTAAATTTTAATAAACAAACTAATAAATCAAATGAAGATATTATTGTAAAAGGCCTTTATGCTGCA GGAGAAGCTGCATCAGCATCTGTTCATGGAGCAAATCGGTTAGGAGCTAATTCACTTTTAGATATTGTCG TTTTTGGTAAAAGAGCTGCACTAACTATTATGGAGATAGATAAACCAAATATTCCTAAAATAAATGCAAA TACTAATATAGGTGAAGAATCTATACAAAGATTAGATCATATAAGATTTAATAAAGGTAGTATACAAACA TCGCAATTAAGAAAAAAAATGCAAATATGCATGCAAAAACATGCTGCTGTTTTTAGAATTGGACCGTTAT TACAAGAAGGTTATAAACAAATTCTTGAAATATGTTCCATTTTTAAAGACATAGAAATTACTGATAAAAC GTTAACATGGAATACAGATTTATTAGAAACATTAGAACTTGAAAATTTACTAACACTCGCATCACAAACT ATCTTAGCAGCTGTTGAAAGAAAAGAATCAAGAGGTGCTCATGCTCGTGACGATTTCCCTGAAAGAGATG ATAAAAACTATTTAAAACATTCCTTAACATGGATGACTGACAGAAATATTGAGAATACAAAATATTTTAC GACTTACAGGGATGTTATAACAAAACCATTAGATAATGAAATGGAATATGTTCCACCTGTTAAACGTGTT TATTAA 32%
 * CDS Gene Sequence (paste as text only):**
 * GC% Content for gene:**
 * CDS Gene Sequence (codon optimized) - copy from output of Primer Design Protocol (paste as text only):**
 * GC% Content for gene (codon optimized):**

Do Not Need this info for Spring (but still copy these lines to your Target page for now) -- Ask a mentor, Dr. B, or a fellow researcher -how to link a GDocs file if you are not sure how to.
 * Primer design results for pNIC-Bsa4 cloning (list seqeunces of all of your ~40 nt long primers):**
 * ( link to DNA Works output text file - **that should be saved in your Google Docs folder after you did the primer design protocol)


 * Primer design results for 'tail' primers (this is just 2 sequences):**

Resources:
See **ProtocolTargetDiscoveryVDS.docx** for more Etiologic Risk Group Categories (for pathogens): http://www.utexas.edu/research/rsc/ibc/agent_class.html#_Toc7238334

@http://www.niaid.nih.gov/Pages/default.aspx @http://eupathdb.org/eupathdb/ @https://patricbrc.vbi.vt.edu/portal/portal/patric/Home @http://www.nmpdr.org/FIG/wiki/view.cgi/Main/EssentialGenes @http://tubic.tju.edu.cn/deg/ @http://csgid.org/csgid/cake/pages/community_request_gateway @http://tdrtargets.org/ @http://gsc.jcvi.org/status.shtml
 * Databases of genes/organisms:**

@http://wwwnc.cdc.gov/eid/pages/scientific-nomenclature.htm
 * Scientific Nomenclature page from Center for Disease Control (gene, protein names and abbreviations)**

NCBI GENE Page: @http://www.ncbi.nlm.nih.gov/gene BLAST Page: @http://blast.ncbi.nlm.nih.gov/
 * Gene Information:**

NCBI Protein Page: @http://www.ncbi.nlm.nih.gov/protein Protein Expression Website Protein Expression Paper:
 * Protein Information:**


 * Primer Overlap PCR Articles**


 * Is my target good for Virtual Screening programs?**


 * References**

[1] Snow, R.W.; Guerra, C.A.; Noor, A.M.; Myint, H.Y.; Hay, S.I., The global distribution of clinical episodes of plasmodium falciparum malaria. //Nature// **2005**, 434, (7030), 214-217.

[2] Hay, S.I.; Guerra, C.A.; Gething, P.W.; Patil, A.P.; Tatem, A.J.; Noor, A.M.; Kabaria, A.M.; Manh, B.H.; Elyazar, I.R.F.; Brooker, S.; Smith, D.L.; Moyeed, R.A.; Snow, R.W., A world malaria map: Plasmodium falciparum endemicity in 2007. //PLoS Med// **2009,** 6, (3).

[3] Bell, D.J.; Molyneux, M.E., Treatment of childhood plasmodium falciparum malaria: Current challenges. //Expert Review of Anti-Infective Therapy// **2007**, 5, (1), 141.