Document Detail

Mechanism for the transport of ammonia within carbamoyl phosphate synthetase determined by molecular dynamics simulations.
MedLine Citation:
PMID:  18220365     Owner:  NLM     Status:  MEDLINE    
Carbamoyl phosphate synthetase (CPS) is a member of the amidotransferase family of enzymes that uses the hydrolysis of glutamine as a localized source of ammonia for biosynthetic transformations. Molecular dynamics simulations for the transfer of ammonia and ammonium through a tunnel in the small subunit of CPS resulted in five successful trajectories for ammonia transfer, while ammonium was immobilized in a water pocket inside the small subunit of the heterodimeric protein. The observed molecular tunnel for ammonia transport is consistent with that suggested by earlier X-ray crystallography and site-directed mutation studies. His-353, Ser-47, and Lys-202, around the active site center in the small subunit, function cooperatively to deliver ammonia from the site of formation to the interface with the large subunit, via the exchange of hydrogen bonds with a critical water cluster within the tunnel. The NH 3 forms and breaks hydrogen bonds to Gly-292, Ser-35, Pro-358, Gly-293, and Thr-37 in a stepwise fashion "macroscopically" as it travels through the hydrophilic passage toward the subunit interface. The potential of mean force calculations along the ammonia transfer pathway indicates a low free-energy path for the translocation of ammonia with two barriers of 3.9 and 5.5 kcal/mol, respectively. These low free-energy barriers are consistent with the delivery of ammonia from the site of formation into a water reservoir toward the exit of the tunnel and migration through the hydrophilic leaving passage, respectively. The high overall free-energy barrier of 22.4 kcal/mol for the transport of ammonium additionally substantiates that the tunnel in the small subunit of CPS is not an ammonium but an ammonia channel.
Yubo Fan; Liliya Lund; Lijiang Yang; Frank M Raushel; Yi-Qin Gao
Related Documents :
24172215 - Fluorescence energy transfer in quantum dot/azo dye complexes in polymer track membranes.
25132195 - Size-dependent thermochromism through enhanced electron-phonon coupling in 1 nm quantum...
24149435 - Excited state electron transfer from aminopyrene to graphene: a combined experimental a...
24016295 - Revealing spectral features in the two-photon absorption spectrum of the hoechst 33342 ...
25023575 - Atomic scale real-space mapping of holes in yba2cu3o6+δ.
21865065 - Evaluation of spin labels for in-cell epr by analysis of nitroxide reduction in cell ex...
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.     Date:  2008-01-26
Journal Detail:
Title:  Biochemistry     Volume:  47     ISSN:  0006-2960     ISO Abbreviation:  Biochemistry     Publication Date:  2008 Mar 
Date Detail:
Created Date:  2008-03-03     Completed Date:  2008-06-04     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0370623     Medline TA:  Biochemistry     Country:  United States    
Other Details:
Languages:  eng     Pagination:  2935-44     Citation Subset:  IM    
Department of Chemistry, Texas A&M University, College Station, Texas 77843, USA.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Ammonia / chemistry*,  metabolism
Binding Sites
Carbamoyl-Phosphate Synthase (Ammonia) / chemistry*,  genetics,  metabolism
Computer Simulation*
Crystallography, X-Ray
Glutamine / chemistry,  metabolism
Protein Binding
Protein Structure, Secondary
Grant Support
Reg. No./Substance:
56-85-9/Glutamine; 7664-41-7/Ammonia; EC Synthase (Ammonia)

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

Previous Document:  Structural changes of eIF4E upon binding to the mRNA 5' monomethylguanosine and trimethylguanosine C...
Next Document:  Monomethylarsonous acid destroys a tetrathiolate zinc finger much more efficiently than inorganic ar...