Despite slow catalysis and confused substrate specificity, all ribulose bisphosphate carboxylases may be nearly perfectly optimized
- Research School of Biological Sciences, Australian National University, Canberra ACT 2601, Australia
-
Edited by George H. Lorimer, University of Maryland, College Park, MD, and approved March 2, 2006 (received for review January 24, 2006)
Abstract
The cornerstone of autotrophy, the CO2-fixing enzyme, d-ribulose-1,5-bisphosphate carboxylase/oxygenase (Rubisco), is hamstrung by slow catalysis and confusion between CO2 and O2 as substrates, an “abominably perplexing” puzzle, in Darwin's parlance. Here we argue that these characteristics stem from difficulty in binding the featureless CO2 molecule, which forces specificity for the gaseous substrate to be determined largely or completely in the transition state. We hypothesize that natural selection for greater CO2/O2 specificity, in response to reducing atmospheric CO2:O2 ratios, has resulted in a transition state for CO2 addition in which the CO2 moiety closely resembles a carboxylate group. This maximizes the structural difference between the transition states for carboxylation and the competing oxygenation, allowing better differentiation between them. However, increasing structural similarity between the carboxylation transition state and its carboxyketone product exposes the carboxyketone to the strong binding required to stabilize the transition state and causes the carboxyketone intermediate to bind so tightly that its cleavage to products is slowed. We assert that all Rubiscos may be nearly perfectly adapted to the differing CO2, O2, and thermal conditions in their subcellular environments, optimizing this compromise between CO2/O2 specificity and the maximum rate of catalytic turnover. Our hypothesis explains the feeble rate enhancement displayed by Rubisco in processing the exogenously supplied carboxyketone intermediate, compared with its nonenzymatic hydrolysis, and the positive correlation between CO2/O2 specificity and 12C/13C fractionation. It further predicts that, because a more product-like transition state is more ordered (decreased entropy), the effectiveness of this strategy will deteriorate with increasing temperature.
Footnotes
- †To whom correspondence should be addressed. E-mail: andrews{at}incanberra.com.au
-
↵*Present address: Laboratoire d'Écophysiologie Végétale, Centre National de la Recherche Scientifique Unité Mixte de Recherche 8079, Université Paris XI, 91405 Orsay, France.
-
Author contributions: G.G.B.T., G.D.F., and T.J.A. designed research, analyzed data, and wrote the paper.
-
See Commentary on page 7203.
-
Conflict of interest statement: No conflicts declared.
-
This paper was submitted directly (Track II) to the PNAS office.
- Abbreviations:
- CABP,
- 2′-carboxy-d-arabinitol 1,5-bisphosphate;
- RuBP,
- d-ribulose 1,5-bisphosphate;
- Rubisco,
- RuBP carboxylase/oxygenase.
Abbreviations:
- © 2006 by The National Academy of Sciences of the USA
