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The planar conformation of a strained proline ring: A QM/MM study
Author(s) -
Donnini Serena,
Groenhof Gerrit,
Wierenga Rik K.,
Juffer André H.
Publication year - 2006
Publication title -
proteins: structure, function, and bioinformatics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.699
H-Index - 191
eISSN - 1097-0134
pISSN - 0887-3585
DOI - 10.1002/prot.21006
Subject(s) - proline , planarity testing , chemistry , triosephosphate isomerase , ring (chemistry) , steric effects , qm/mm , crystallography , stereochemistry , molecular dynamics , amino acid , computational chemistry , biochemistry , organic chemistry , gene
QM and QM/MM energy calculations have been carried out on an atomic resolution structure of liganded triosephosphate isomerase (TIM) that has an active site proline (Pro168) in a planar conformation. The origin of the planarity of this proline has been identified. Steric interactions between the atoms of the proline ring and a tyrosine ring (Tyr166) on one side of the proline prevent the ring from adopting the up pucker (χ 1 is approximately −30°), while the side chain of a nearby alanine (Ala171) forbids the down pucker (χ 1 is approximately +30°). To obtain a proline conformation that is in agreement with the experimentally observed planar state, a quantum system of sufficient size is required and should at least include the nearby side chains of Tyr166, Ala171, and Glu129 to provide enough stabilization. It is argued that the current force fields for structure optimization do not describe strained protein fragments correctly. The proline is part of a catalytic loop that closes upon ligand binding. Comparison of the proline conformation in different TIM X‐ray structures, indicates that in the closed conformation of TIM the proline is planar or nearly planar, while in the open conformation it is down puckered. This suggests that the planarity possibly plays a role in the overall catalytic cycle of TIM, presumable acting as a reservoir of energy that becomes available upon loop opening. Proteins 2006. © 2006 Wiley‐Liss, Inc.