Linked Life Data

19028476

Source:http://linkedlifedata.com/resource/pubmed/id/19028476

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1-3
pubmed:dateCreated
2009-2-9
pubmed:abstractText
In NAD(P)-dependent enzymes the coenzyme gives or takes a hydride ion, but how the nicotinamide ring is activated to form the transition state for hydride transfer is not clear. On the basis of ultra-high resolution X-ray crystal structures of liver alcohol dehydrogenase (LADH) in complex with NADH and a number of substrate analogues we proposed that the activation of NADH is an integral part of the enzyme mechanism of aldehyde reduction [R. Meijers, R.J. Morris, H.W. Adolph, A. Merli, V.S. Lamzin, E.S. Cedergren-Zeppezauer, On the enzymatic activation of NADH, The Journal of Biological Chemistry 276(12) (2001) 9316-9321, %U http://www.ncbi.nlm.nih.gov/pubmed/11134046; R. Meijers, H.-W. Adolph, Z. Dauter, K.S. Wilson, V.S. Lamzin, E.S. Cedergren-Zeppezauer, Structural evidence for a ligand coordination switch in liver alcohol dehydrogenase, Biochemistry 46(18) (2007) 5446-5454, %U http://www.ncbi.nlm.nih.gov/pubmed/17429946]. We observed a nicotinamide with a severely distorted pyridine ring and a water molecule in close proximity to the ring. Quantum chemical calculations indicated that (de)protonation of the water molecule can be directly coupled to activation of NADH for hydride transfer. A systematic search of the Protein Data Bank (PDB) for atoms that come within van der Waals distance of the pyridine ring of the nicotinamide reveals that a large number of NAD(P)-containing protein complexes are involved in electrostatic interactions with the enzymatic environment. Using the deposited diffraction data to analyze the cofactor and its surroundings, we observe several adducts between protein atoms and the pyridine ring that were not previously reported. This further indicates that the enzymatic activation of NAD(P) induced by electrostatic interactions is an essential part of the hydride transfer mechanism.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
1872-7786
pubmed:author
pubmed:issnType
Electronic
pubmed:day
16
pubmed:volume
178
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
24-8
pubmed:meshHeading
pubmed:year
2009
pubmed:articleTitle
A variety of electrostatic interactions and adducts can activate NAD(P) cofactors for hydride transfer.
pubmed:affiliation
Synchrotron Soleil, L'Orme des Merisiers, Saint Aubin, France. rob.meijers@synchrotron-soleil.fr
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't