Please contact us for any questions or request for reagents for this structure.

Human Cysteine Sulfinic Acid Decarboxylase in complex with PLP

Click on the iSee icon to launch an enhanced annotation with interactive 3D representations and animated transitions. Please note that a web plugin (activeICM) is required to access this enhanced functionality. Instructions for the installation and use of the web plugin are available.

PDB Code 2JIS Target Class AA metabolic enzymes Target CSAD Alias CSAD, CSD, FLJ44987, FLJ45500, MGC119354, MGC119355, MGC119357, PCAP Disease Area/Function cancer Date Deposited Jun 30 2007 Authors R.COLLINS, M.MOCHE, C.ARROWSMITH, H.BERGLUND, R.BUSAM, L.G.DAHLGREN, A.EDWARDS, S.FLODIN, A.FLORES, S.GRASLUND, M.HAMMARSTROM, B.M.HALLBERG, I.JOHANSSON, A.KALLAS, T.KARLBERG, T.KOTENYOVA, L.LEHTIO, P.NORDLUND, T.NYMAN, D.OGG, C.PERSSON, J.SAGEMARK, P.STENMARK, M.SUNDSTROM, A.G.THORSELL, L.TRESAUGUES, S.VAN-DEN-BERG, J.WEIGELT, M.WELIN, L.HOLMBERG-SCHIAVONE

About this structure

The amino sulphonic acid taurine, is one of the most abundant amino acids in the brain. Originally thought to be just the end product of cysteine metabolism, it has been found to be essential to a number of biological processes such as development of the brain and eye, reproduction, diabetes, osmoregulation as well as the anti-inflammatory activity of leukocytes.

Cysteine sulfinic acid decarboxylase (CSAD) catalyses the penultimate and rate limiting step of taurine synthesis. Cysteine dioxygenase catalyses the production of its substrate, cysteine sulfinic acid, by the oxidization of the sulfhydryl moiety of cysteine. CSAD subsequently decarboxylates the cysteine sulfinic acid producing hypotaurine. While, in vitro, Glutamate decarboxylase (GAD) has been observed to contribute to decarboxylation of cysteine sulfinic acid, CSAD provides the principle activity in vivo in both liver and brain. Hypotaurine is further oxidized to taurine by a putative hypotaurine dehydrogenase.

We have solved the structure of CSAD to a resolution of 1.6Å by de novo phasing using selenomethionine labeled protein. The enzyme crystallized as a homo-dimer with the co-factor Pyridoxal 5’phosphate (PLP) bound through a Schiff base to lysine 305 in both monomers. A nitrate molecule was clearly seen in the electron density, coordinated to His431, Trp 415, Gly462 and Arg461, which may stabilize the loop containing the latter two amino acids. The active site cavity is formed by both monomers. Within both active sites the loop containing Cys190, His191 and Tyr192 has been modeled in two alternative conformations. Part of the putative catalytic loop from Lys341 to Ser331 in chain A is unstructured while in chain B it is modeled in a much more open conformation when compared to the structurally and functionally similar GAD. This overall relaxed formation of the active site may reflect the absence of a bound substrate or product molecule in the CSAD structure.

References

  1. Tappaz M., Admarghini K., Legay F., and Remy A. (1992) Taurine biosynthesis enzyme cysteine sulfinate decarboxylase (CSD) from brain: the long and tricky trail to identification. Neurochemical Research, VoL 17, No. 9, pp. 849-859
  2. Park E, Park SY, Wang C, Xu J, LaFauci G, Schuller-Levis G.(2002) Cloning of murine cysteine sulfinic acid decarboxylase and its mRNA expression in murine tissues. Biochim. Biophys. Acta. Apr 12;1574(3):403-6.
  3. Tang XW, Hsu CC, Schloss JV, Faiman MD, Wu E, Yang CY, Wu JY. (1997) Protein phosphorylation and taurine biosynthesis in vivo and in vitro. J. Neurosci. Sep 15;17(18):6947-51.
  4. Fenalti G, Law RH, Buckle AM, Langendorf C, Tuck K, Rosado CJ, Faux NG, Mahmood K, Hampe CS, Banga JP, Wilce M, Schmidberger J, Rossjohn J, El-Kabbani O, Pike RN, Smith AI, Mackay IR, Rowley MJ, Whisstock JC.(2007) GABA production by glutamic acid decarboxylase is regulated by a dynamic catalytic loop. Nat. Struct. Mol. Biol. Apr;14(4):280-6. Epub 2007 Mar 25.