3ia4
Moritella profunda dihydrofolate reductase (DHFR) in complex with NADPH and methotrexate (MTX)Moritella profunda dihydrofolate reductase (DHFR) in complex with NADPH and methotrexate (MTX)
Structural highlights
Function[Q70YQ6_MORPR] Key enzyme in folate metabolism. Catalyzes an essential reaction for de novo glycine and purine synthesis, and for DNA precursor synthesis (By similarity).[PIRNR:PIRNR000194] Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedWe report the crystal structure of dihydrofolate reductase (DHFR) from the psychropiezophilic bacterium Moritella profunda, which was isolated from the deep ocean at 2 degrees C and 280 bar. The structure is typical of a chromosomal DHFR and we were unable to identify any obvious structural features that would suggest pressure adaptation. In particular, the core regions of the enzyme are virtually identical to those of the DHFR from the mesophile Escherichia coli. The steady-state rate at pH 9, which is limited by hydride transfer at atmospheric pressure, is roughly constant between 1 and 750 bar, falling at higher pressures. However, the value of K(M) increases with increasing pressure, and as a result k(cat)/K(M) decreases over the entire pressure range studied. Isotope effect studies showed that increasing the pressure causes a change in the rate-limiting step of the reaction. We therefore see no evidence of pressure adaptation in either the structure or the activity of this enzyme. Are the Catalytic Properties of Enzymes from Piezophilic Organisms Pressure Adapted?,Hay S, Evans RM, Levy C, Loveridge EJ, Wang X, Leys D, Allemann RK, Scrutton NS Chembiochem. 2009 Aug 13. PMID:19681091[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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