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PDBsum entry 1ai3
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Oxidoreductase
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PDB id
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1ai3
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References listed in PDB file
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Key reference
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Title
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Orbital steering in the catalytic power of enzymes: small structural changes with large catalytic consequences.
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Authors
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A.D.Mesecar,
B.L.Stoddard,
D.E.Koshland.
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Ref.
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Science, 1997,
277,
202-206.
[DOI no: ]
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PubMed id
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Abstract
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Small structural perturbations in the enzyme isocitrate dehydrogenase (IDH) were
made in order to evaluate the contribution of precise substrate alignment to the
catalytic power of an enzyme. The reaction trajectory of IDH was modified (i)
after the adenine moiety of nicotinamide adenine dinucleotide phosphate was
changed to hypoxanthine (the 6-amino was changed to 6-hydroxyl), and (ii) by
replacing Mg2+, which has six coordinating ligands, with Ca2+, which has eight
coordinating ligands. Both changes make large (10(-3) to 10(-5)) changes in the
reaction velocity but only small changes in the orientation of the substrates
(both distance and angle) as revealed by cryocrystallographic trapping of active
IDH complexes. The results provide evidence that orbital overlap produced by
optimal orientation of reacting orbitals plays a major quantitative role in the
catalytic power of enzymes.
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Figure 1.
Fig. 1. Orbital steering in enzyme-catalyzed reactions can
lead (A) to properly aligned substrates by maximizing bonding
orbital overlaps and minimizing anti-bonding orbital overlaps or
can lead^ (B) to improperly aligned substrates if the reaction
coordinate^ trajectory is perturbed by modification.
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Figure 2.
Fig. 2. Schematic illustration of NADP and NHDP.
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The above figures are
reprinted
by permission from the AAAs:
Science
(1997,
277,
202-206)
copyright 1997.
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Secondary reference #1
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Title
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Determinants of cofactor specificity in isocitrate dehydrogenase: structure of an engineered NADP+ --≫ NAD+ specificity-Reversal mutant.
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Authors
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J.H.Hurley,
R.Chen,
A.M.Dean.
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Ref.
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Biochemistry, 1996,
35,
5670-5678.
[DOI no: ]
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PubMed id
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Secondary reference #2
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Title
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Structure of isocitrate dehydrogenase with isocitrate, Nicotinamide adenine dinucleotide phosphate, And calcium at 2.5-A resolution: a pseudo-Michaelis ternary complex.
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Authors
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B.L.Stoddard,
A.Dean,
D.E.Koshland.
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Ref.
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Biochemistry, 1993,
32,
9310-9316.
[DOI no: ]
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PubMed id
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