PMID- 10053003 OWN - NLM STAT- MEDLINE DCOM- 19990420 LR - 20211203 IS - 0002-9297 (Print) IS - 0002-9297 (Linking) VI - 64 IP - 3 DP - 1999 Mar TI - Human molybdopterin synthase gene: identification of a bicistronic transcript with overlapping reading frames. PG - 698-705 AB - A universal molybdenum-containing cofactor (MoCo) is essential for the activity of all human molybdoenzymes, including sulphite oxidase. The free cofactor is highly unstable, and all organisms share a similar biosynthetic pathway. The involved enzymes exhibit homologies, even between bacteria and humans. We have exploited these homologies to isolate a cDNA for the heterodimeric molybdopterin (MPT)-synthase. This enzyme is necessary for the conversion of an unstable precursor into molybdopterin, the organic moiety of MoCo. The corresponding transcript shows a bicistronic structure, encoding the small and large subunits of the MPT-synthase in two different open reading frames (ORFs) that overlap by 77 nucleotides. In various human tissues, only one size of mRNA coinciding with the bicistronic transcript was detected. In vitro translation and mutagenesis experiments demonstrated that each ORF is translated independently, leading to the synthesis of a 10-kDa protein and a 21-kDa protein for the small and large subunits, respectively, and indicated that the 3'-proximal ORF of the bicistronic transcript is translated by leaky scanning. FAU - Stallmeyer, B AU - Stallmeyer B AD - Botanisches Institut der Technischen Universitat, Braunschweig, Humboldtstr. 1, D-38106 Braunschweig, Germany. FAU - Drugeon, G AU - Drugeon G FAU - Reiss, J AU - Reiss J FAU - Haenni, A L AU - Haenni AL FAU - Mendel, R R AU - Mendel RR LA - eng SI - GENBANK/AF091871 SI - GENBANK/AF091872 SI - GENBANK/D64003 SI - GENBANK/U21322 SI - GENBANK/U29587 SI - GENBANK/U88180 SI - GENBANK/X70420 PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - Am J Hum Genet JT - American journal of human genetics JID - 0370475 RN - 0 (Coenzymes) RN - 0 (Metalloproteins) RN - 0 (Molybdenum Cofactors) RN - 0 (Pteridines) RN - 86-01-1 (Guanosine Triphosphate) RN - ATN6EG42UQ (molybdenum cofactor) RN - EC 2.8.1.- (Sulfurtransferases) RN - EC 2.8.1.- (molybdopterin synthase) SB - IM MH - Amino Acid Sequence MH - Animals MH - Base Sequence MH - Blotting, Northern MH - *Coenzymes MH - Escherichia coli/genetics MH - Gene Library MH - Genes, Overlapping MH - Guanosine Triphosphate/metabolism MH - Humans MH - Liver/metabolism MH - Metalloproteins/metabolism MH - Molecular Sequence Data MH - Molybdenum Cofactors MH - Mutagenesis, Insertional MH - Protein Biosynthesis/physiology MH - Pteridines/metabolism MH - Rabbits MH - Reading Frames/genetics MH - Reticulocytes/metabolism MH - Sequence Homology, Amino Acid MH - Sulfurtransferases/*genetics PMC - PMC1377786 EDAT- 1999/03/03 03:04 MHDA- 2000/03/21 09:00 CRDT- 1999/03/03 03:04 PHST- 1999/03/03 03:04 [pubmed] PHST- 2000/03/21 09:00 [medline] PHST- 1999/03/03 03:04 [entrez] AID - S0002-9297(07)61706-6 [pii] AID - 10.1086/302295 [doi] PST - ppublish SO - Am J Hum Genet. 1999 Mar;64(3):698-705. doi: 10.1086/302295.