Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:1.1.1.28 (lactic acid dehydrogenase)
 476 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have adapted a LacZ promoter trap screen developed by Burns et al. (1994) to search for genes whose expression is dependent on Rtg2p, a protein with an N-terminal hsp70/actin/sugar kinase ATP binding domain. Rtg2p acts upstream of the basic helix-loop-helix/leucine zipper transcription factors, Rtg1p and Rtg3p. All three proteins are known to be required for the expression of the CIT2 gene, which encodes a peroxisomal isoform of citrate synthase whose expression is also dependent on the functional state of mitochondria. Using this screen, we have identified a previously uncharacterized gene, YEL071w, predicted to encode a protein of 496 amino acids that shares 80% homology and 60% sequence identity with actin interacting protein 2, encoded by the AIP2 gene; both proteins also share sequence similarity to aD-lactate dehydrogenase encoded by the DLD1 gene. Expression of YEL071w is dependent on the functional state of mitochondria and on all three of the Rtg proteins, whereas AIP2 expression is independent of the Rtg proteins and the functional state of mitochondria. Like CIT2, the 5' flanking region of YEL071w contains two R box binding sites for the Rtg1p/Rtg3p heterodimeric transcription complex. Both R boxes are necessary for full YEL071w expression. We show that YEL071w and AIP2 encode proteins withD-lactate dehydrogenase activity, the former located in the cytoplasm and the latter in the mitochondrial matrix. Our data thus provide gene assignments for two previously unrecognized D-lactate dehydrogenase activities in yeast.
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PMID:Signalling between mitochondria and the nucleus regulates the expression of a new D-lactate dehydrogenase activity in yeast. 1050 19

Mammalian L-isomer dehydrogenases represent an expansive and well characterized class of metabolic enzymes. Surprisingly, little is known regarding their evolutionarily distinct counterparts, D-isomer dehydrogenases, since few mammalian D-isomer 2-hydroxy acid enzymes have been isolated. Here we present the identification and initial characterization of putative human and murine D-lactate dehydrogenases (DLD) that can interact with the muscle-specific cysteine-rich protein CRP3/MLP. Sequence analysis reveals that the human and mouse transcripts encode novel proteins that display strong similarities to the yeast D-lactate dehydrogenase proteins DLD1, AIP2, and YEL071W. Expression analysis of the mammalian proteins indicates widespread distribution with transcripts present in striated muscle tissues and a variety of other tissue types. Immunofluorescence subcellular localization of the mouse DLD protein indicates that it resides within mitochondria, a feature shared by many dehydrogenases. The identification of the human and mouse DLD clones provides new insight regarding the activity of D-isomer-specific enzymes in mammalian cells.
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PMID:Identification of putative mammalian D-lactate dehydrogenase enzymes. 1212 81