Isocitrate lyase

Details

Name
Isocitrate lyase
Synonyms
  • 4.1.3.1
  • ICL
  • Isocitrase
  • Isocitratase
Gene Name
icl
Organism
Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv)
Amino acid sequence
>lcl|BSEQ0051124|Isocitrate lyase
MSVVGTPKSAEQIQQEWDTNPRWKDVTRTYSAEDVVALQGSVVEEHTLARRGAEVLWEQL
HDLEWVNALGALTGNMAVQQVRAGLKAIYLSGWQVAGDANLSGHTYPDQSLYPANSVPQV
VRRINNALQRADQIAKIEGDTSVENWLAPIVADGEAGFGGALNVYELQKALIAAGVAGSH
WEDQLASEKKCGHLGGKVLIPTQQHIRTLTSARLAADVADVPTVVIARTDAEAATLITSD
VDERDQPFITGERTREGFYRTKNGIEPCIARAKAYAPFADLIWMETGTPDLEAARQFSEA
VKAEYPDQMLAYNCSPSFNWKKHLDDATIAKFQKELAAMGFKFQFITLAGFHALNYSMFD
LAYGYAQNQMSAYVELQEREFAAEERGYTATKHQREVGAGYFDRIATTVDPNSSTTALTG
STEEGQFH
Number of residues
428
Molecular Weight
47086.255
Theoretical pI
Not Available
GO Classification
Functions
isocitrate lyase activity / metal ion binding / methylisocitrate lyase activity / zymogen binding
Processes
cellular response to hypoxia / glyoxylate cycle / isocitrate metabolic process / maintenance of symbiont tolerance to host environment / pathogenesis / response to acetate / response to acid chemical / response to fatty acid / response to host immune response / tricarboxylic acid cycle
Components
cytosol / extracellular region / plasma membrane
General Function
Involved in the persistence and virulence of M.tuberculosis. Catalyzes the reversible formation of succinate and glyoxylate from isocitrate, a key step of the glyoxylate cycle, which operates as an anaplerotic route for replenishing the tricarboxylic acid cycle during growth on fatty acid substrates (PubMed:10932251, PubMed:10963599, PubMed:18275086, PubMed:24354272). It could also catalyze the formation of pyruvate and succinate from 2-methylisocitrate, a key step in the methylcitrate cycle (propionate degradation route) (By similarity).
Specific Function
Isocitrate lyase activity
Pfam Domain Function
Transmembrane Regions
Not Available
Cellular Location
Not Available
Gene sequence
>lcl|BSEQ0051125|Isocitrate lyase (icl)
ATGTCTGTCGTCGGCACCCCGAAGAGCGCGGAGCAGATCCAGCAGGAATGGGACACGAAC
CCGCGCTGGAAGGACGTCACCCGCACCTACTCCGCCGAGGACGTCGTCGCCCTCCAGGGC
AGCGTGGTCGAGGAGCACACGCTGGCCCGCCGCGGTGCGGAGGTGCTGTGGGAGCAGCTG
CACGACCTCGAGTGGGTCAACGCGCTGGGCGCGCTGACCGGCAACATGGCCGTCCAGCAG
GTGCGCGCCGGCCTGAAGGCCATCTACCTGTCGGGCTGGCAGGTCGCCGGCGATGCCAAC
CTGTCCGGGCACACCTACCCCGACCAGAGCCTGTATCCCGCCAACTCGGTGCCGCAGGTG
GTCCGCCGGATCAACAACGCACTGCAGCGCGCCGACCAGATCGCCAAGATCGAGGGCGAT
ACTTCGGTGGAGAACTGGCTGGCGCCGATTGTCGCCGACGGCGAGGCCGGCTTTGGCGGC
GCGCTCAACGTCTACGAGCTGCAGAAAGCCCTGATCGCCGCGGGCGTTGCGGGTTCGCAC
TGGGAGGACCAGTTGGCCTCTGAGAAGAAGTGCGGCCACCTGGGCGGCAAGGTGTTGATC
CCGACCCAGCAGCACATCCGCACTTTGACGTCTGCTCGGCTCGCGGCCGATGTGGCTGAT
GTTCCCACGGTGGTGATCGCCCGTACCGACGCCGAGGCGGCCACGCTGATCACCTCCGAC
GTCGACGAGCGCGACCAGCCGTTCATCACCGGCGAGCGCACCCGGGAAGGCTTCTACCGC
ACCAAGAACGGCATCGAGCCTTGCATCGCTCGGGCGAAGGCCTACGCCCCGTTCGCCGAC
TTGATCTGGATGGAGACCGGTACCCCGGACCTCGAGGCCGCCCGGCAGTTCTCCGAGGCG
GTCAAGGCGGAGTACCCGGACCAGATGCTGGCCTACAACTGCTCGCCATCGTTCAACTGG
AAAAAGCACCTCGACGACGCCACCATCGCCAAGTTCCAGAAGGAGCTGGCAGCCATGGGC
TTCAAGTTCCAGTTCATCACGCTGGCCGGCTTCCATGCGCTGAACTACTCGATGTTCGAT
CTGGCCTACGGCTACGCCCAGAACCAGATGAGCGCGTATGTCGAACTGCAGGAACGCGAG
TTCGCCGCCGAAGAACGGGGCTACACCGCGACCAAGCACCAGCGCGAGGTCGGCGCCGGC
TACTTCGACCGGATTGCCACCACCGTGGACCCGAATTCGTCGACCACCGCGTTGACCGGT
TCCACCGAAGAGGGCCAGTTCCACTAG
Chromosome Location
Not Available
Locus
Not Available
External Identifiers
ResourceLink
UniProtKB IDP9WKK7
UniProtKB Entry NameACEA_MYCTU
General References
  1. Cole ST, Brosch R, Parkhill J, Garnier T, Churcher C, Harris D, Gordon SV, Eiglmeier K, Gas S, Barry CE 3rd, Tekaia F, Badcock K, Basham D, Brown D, Chillingworth T, Connor R, Davies R, Devlin K, Feltwell T, Gentles S, Hamlin N, Holroyd S, Hornsby T, Jagels K, Krogh A, McLean J, Moule S, Murphy L, Oliver K, Osborne J, Quail MA, Rajandream MA, Rogers J, Rutter S, Seeger K, Skelton J, Squares R, Squares S, Sulston JE, Taylor K, Whitehead S, Barrell BG: Deciphering the biology of Mycobacterium tuberculosis from the complete genome sequence. Nature. 1998 Jun 11;393(6685):537-44. [Article]
  2. McKinney JD, Honer zu Bentrup K, Munoz-Elias EJ, Miczak A, Chen B, Chan WT, Swenson D, Sacchettini JC, Jacobs WR Jr, Russell DG: Persistence of Mycobacterium tuberculosis in macrophages and mice requires the glyoxylate shunt enzyme isocitrate lyase. Nature. 2000 Aug 17;406(6797):735-8. [Article]
  3. Kumar R, Bhakuni V: Mycobacterium tuberculosis isocitrate lyase (MtbIcl): role of divalent cations in modulation of functional and structural properties. Proteins. 2008 Aug 15;72(3):892-900. doi: 10.1002/prot.21984. [Article]
  4. Festa RA, McAllister F, Pearce MJ, Mintseris J, Burns KE, Gygi SP, Darwin KH: Prokaryotic ubiquitin-like protein (Pup) proteome of Mycobacterium tuberculosis [corrected] . PLoS One. 2010 Jan 6;5(1):e8589. doi: 10.1371/journal.pone.0008589. [Article]
  5. Kelkar DS, Kumar D, Kumar P, Balakrishnan L, Muthusamy B, Yadav AK, Shrivastava P, Marimuthu A, Anand S, Sundaram H, Kingsbury R, Harsha HC, Nair B, Prasad TS, Chauhan DS, Katoch K, Katoch VM, Kumar P, Chaerkady R, Ramachandran S, Dash D, Pandey A: Proteogenomic analysis of Mycobacterium tuberculosis by high resolution mass spectrometry. Mol Cell Proteomics. 2011 Dec;10(12):M111.011627. doi: 10.1074/mcp.M111.011445. Epub 2011 Oct 3. [Article]
  6. Moynihan MM, Murkin AS: Cysteine is the general base that serves in catalysis by isocitrate lyase and in mechanism-based inhibition by 3-nitropropionate. Biochemistry. 2014 Jan 14;53(1):178-87. doi: 10.1021/bi401432t. Epub 2013 Dec 24. [Article]
  7. Sharma V, Sharma S, Hoener zu Bentrup K, McKinney JD, Russell DG, Jacobs WR Jr, Sacchettini JC: Structure of isocitrate lyase, a persistence factor of Mycobacterium tuberculosis. Nat Struct Biol. 2000 Aug;7(8):663-8. [Article]
  8. Micklinghoff JC, Breitinger KJ, Schmidt M, Geffers R, Eikmanns BJ, Bange FC: Role of the transcriptional regulator RamB (Rv0465c) in the control of the glyoxylate cycle in Mycobacterium tuberculosis. J Bacteriol. 2009 Dec;191(23):7260-9. doi: 10.1128/JB.01009-09. Epub 2009 Sep 18. [Article]
  9. Masiewicz P, Brzostek A, Wolanski M, Dziadek J, Zakrzewska-Czerwinska J: A novel role of the PrpR as a transcription factor involved in the regulation of methylcitrate pathway in Mycobacterium tuberculosis. PLoS One. 2012;7(8):e43651. doi: 10.1371/journal.pone.0043651. Epub 2012 Aug 16. [Article]

Drug Relations

Drug Relations
DrugBank IDNameDrug groupPharmacological action?ActionsDetails
DB04343Glyoxylic acidexperimentalunknownDetails