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

Human alanine aminotransferase 2 in complex with PLP

PDB Code 3IHJ Target Class AA metabolic enzymes Target GPT2 Alias ALT2, GPT2 Disease Area/Function metabolism Date Deposited Jul 30 2009 Authors Wisniewska, M. Siponen, M.I. Arrowsmith, C.H. Berglund, H. Bountra, C. Collins, R. Edwards, A.M. Flodin, S. Flores, A. Graslund, S. Hammarstrom, M. Johansson, A. Johansson, I. Karlberg, T. Kotenyova, T. Kotzsch, A. Markova, N. Moche, M. Nielsen, T.K. Nordlund, P. Nyman, T. Persson, C. Roos, A.K. Schutz, P. Svensson, L. Thorsell, A.G. Tresaugues, L. Van Den Berg, S. Wahlberg E. Weigelt, J. Welin, M. Schuler, H.

About this structure

Alanine aminotransferase (ALT, ALAT; EC 2.6.1.2., formerly called glutamate–pyruvate transaminase [GPT]), is a pyridoxal phosphate dependent enzyme that catalyzes the reversible transamination between alanine and 2-oxoglutarate to form pyruvate and glutamate. By mediating the conversion of these four major intermediate metabolites, this transaminase plays an important role in gluconeogenesis and in amino acid metabolism, particularly during fasting and exercise where glucose is made from pyruvate converted from alanine through de-transamination by ALT [1].

Catalytic activity: L-alanine + 2-oxoglutarate = pyruvate + L-glutamate

Recently, two isoforms of ALT, each encoded by a different gene, have been identified in human and mouse with distinct tissue expression at the mRNA level. ALT1 is mainly expressed in intestine, liver, kidney, and heart, whereas ALT2 is mainly expressed in muscle, brain, fat, kidney and liver [2], suggesting a functional difference in biology between the isoenzymes. Determination of serum ALT activity is one of the most widely used assays in clinical chemistry. An elevated serum ALT activity is regarded as evidence of liver damage, including hepatitis, nonalcoholic steatohepatosis, fatty liver, cirrhosis, and drug hepatoxicity [3]. Serum ALT elevation is also observed in extra-hepatic diseases, such as muscle disease and obesity [4], and in apparently healthy people [5].

Here we present the crystal structure of human ALAT2 (residues Thr49 to Ala523) in complex with pyridoxal phosphate (PLP) at a resolution of 2.3Å.

References

  1. P. Felig (1973) The glucose–alanine cycle. Metabolism 22, 179–207. PubMed 4567003
  2. R.Z. Yang, G. Blaileanu, B.C. Hansen, A.R. Shuldiner and D.W. Gong (2002) Genomics 79, 445–450. PubMed 11863375
  3. D.R. Dufour, J.A. Lott, F.S. Nolte, D.R. Gretch, R.S. Koff and L.B. Seeff (2000) Diagnosis and monitoring of hepatic injury. I. Performance characteristics of laboratory tests. Clin. Chem. 46, 2027–2049. PubMed 11106349
  4. C.E. Ruhl and J.E. Everhart (2003) Relation of elevated serum alanine aminotransferase activity with iron and antioxidant levels in the United States. Gastroenterology 124, 1821–1829. PubMed 12806616
  5. D.E. Johnston (1999) Special considerations in interpreting liver function tests, Am. Fam. Physician 59, 2223–2230. PubMed 10221307