ArticleProceedings of the National Academy of Sciences of the United States of America1999
A bicarbonate ion as a general base in the mechanism of peptide hydrolysis by dizinc leucine aminopeptidase.
Article in Proceedings of the National Academy of Sciences of the United States of America, 1999. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
24 citing papers in PubMed, 103 citations in OpenAlex.
- A SecA-associated protease modulates the extent of surface display of staphylococcal protein A.Journal of bacteriology · 2025Article
- Unveiling the Catalytic Mechanism of a Processive Metalloaminopeptidase.Biochemistry · 2023Article
- Formation of Unstable and very Reactive Chemical Species Catalyzed by Metalloenzymes: A Mechanistic Overview.Molecules (Basel, Switzerland) · 2019Review
- Critical Influence of Cosolutes and Surfaces on the Assembly of Serpin-Derived Amyloid Fibrils.Biophysical journal · 2017Article
- A small unstructured region in Vibrio cholerae ToxT mediates the response to positive and negative effectors and ToxT proteolysis.Journal of bacteriology · 2015Article
- Structures of bacterial kynurenine formamidase reveal a crowded binuclear zinc catalytic site primed to generate a potent nucleophile.The Biochemical journal · 2014Article
- Structural basis of the induced-fit mechanism of 1,4-dihydroxy-2-naphthoyl coenzyme A synthase from the crotonase fold superfamily.PloS one · 2013Article
- Plant leucine aminopeptidases moonlight as molecular chaperones to alleviate stress-induced damage.The Journal of biological chemistry · 2012Article
- Differential domain structure stability of the severe acute respiratory syndrome coronavirus papain-like protease.Archives of biochemistry and biophysics · 2012Article
- Mechanism of peptide hydrolysis by co-catalytic metal centers containing leucine aminopeptidase enzyme: a DFT approach.Journal of biological inorganic chemistry : JBIC : a publication of the Society of Biological Inorganic Chemistry · 2012Article
- Structural evidence for a copper-bound carbonate intermediate in the peroxidase and dismutase activities of superoxide dismutase.PloS one · 2012Article
- Oligopeptide permease A5 modulates vertebrate host-specific adaptation of Borrelia burgdorferi.Infection and immunity · 2011Article
- Applications of analytical ultracentrifugation to protein size-and-shape distribution and structure-and-function analyses.Methods (San Diego, Calif.) · 2011Article
- Expansion and functional diversification of a leucyl aminopeptidase family that encodes the major protein constituents of Drosophila sperm.BMC genomics · 2011Article
- A bicarbonate cofactor modulates 1,4-dihydroxy-2-naphthoyl-coenzyme a synthase in menaquinone biosynthesis of Escherichia coli.The Journal of biological chemistry · 2010Article
- Mutation of Glu-166 blocks the substrate-induced dimerization of SARS coronavirus main protease.Biophysical journal · 2010Article
- Bicarbonate Induces Vibrio cholerae virulence gene expression by enhancing ToxT activity.Infection and immunity · 2009Article
- New role for leucyl aminopeptidase in glutathione turnover.The Biochemical journal · 2004Article
- DapE can function as an aspartyl peptidase in the presence of Mn2+.Journal of bacteriology · 2003Article
- Isolation and characterization of the neutral leucine aminopeptidase (LapN) of tomato.Plant physiology · 2003Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 3 institutions in 2 countries.
Funding
Abstract
The active sites of aminopeptidase A (PepA) from Escherichia coli and leucine aminopeptidase from bovine lens are isostructural, as shown by x-ray structures at 2.5 A and 1.6 A resolution, respectively. In both structures, a bicarbonate anion is bound to an arginine side chain (Arg-356 in PepA and Arg-336 in leucine aminopeptidase) very near two catalytic zinc ions. It is shown that PepA is activated about 10-fold by bicarbonate when L-leucine p-nitroanilide is used as a substrate. No activation by bicarbonate ions is found for mutants R356A, R356K, R356M, and R356E of PepA. In the suggested mechanism, the bicarbonate anion is proposed to facilitate proton transfer from a zinc-bridging water nucleophile to the peptide leaving group. Thus, the function of the bicarbonate ion as a general base is similar to the catalytic role of carboxylate side chains in the presumed mechanisms of other dizinc or monozinc peptidases. A mutational analysis shows that Arg-356 influences activity by binding the bicarbonate ion but is not essential for activity. Mutation of the catalytic Lys-282 reduces k(cat)/K(m) about 10,000-fold.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.