Differences in catalytic activity between rat testicular and ovarian carbonyl reductases are due to two amino acids

Sciotti, Michel A; Tam, Steven; Wermuth, Bendicht; Baker, Michael E (2006). Differences in catalytic activity between rat testicular and ovarian carbonyl reductases are due to two amino acids. FEBS letters, 580(1), pp. 67-71. Amsterdam: Elsevier 10.1016/j.febslet.2005.11.049

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The sequences of rat testis carbonyl reductase (rCR1) and rat ovary carbonyl reductase (rCR2) are 98% identical, differing only at amino acids 140, 141, 143, 235 and 238. Despite such strong sequence identity, we find that rCR1 and rCR2 have different catalytic constants for metabolism of menadione and 4-benzoyl-pyridine. Compared to rCR1, rCR2 has a 20-fold lower K(m) and 5-fold lower k(cat) towards menadione and a 7-fold lower K(m) and 7-fold lower k(cat) towards 4-benzoyl-pyridine. We constructed hybrids of rCR1 and rCR2 that were changed at either residues 140, 141 and 143 or residues 235 and 238. rCR1 with residues 140, 141 and 143 of rCR2 has similar catalytic efficiency for menadione and 4-benzoyl-pyridine as rCR1. rCR1 with Thr-235 and Glu-238 of rCR2 has the catalytic constants of rCR2, indicating that it is this part of rCR2 that contributes to its lower K(m) for menadione and 4-benzoyl-pyridine. Comparisons of three-dimensional models of rCR1 and rCR2 show how Thr-235 and Glu-238 stabilize rCR2 binding of NADPH and menadione.

Item Type:	Journal Article (Original Article)
Division/Institute:	04 Faculty of Medicine > Department of Haematology, Oncology, Infectious Diseases, Laboratory Medicine and Hospital Pharmacy (DOLS) > Institute of Clinical Chemistry
UniBE Contributor:	Sciotti, MA, Wermuth, Bendicht
ISSN:	0014-5793
ISBN:	16359670
Publisher:	Elsevier
Language:	English
Submitter:	Factscience Import
Date Deposited:	04 Oct 2013 14:46
Last Modified:	05 Dec 2022 14:14
Publisher DOI:	10.1016/j.febslet.2005.11.049
PubMed ID:	16359670
Web of Science ID:	000234605100013
URI:	https://boris.unibe.ch/id/eprint/19139 (FactScience: 1528)