Predicting protein decomposition: the case of aspartic-acid racemization kinetics
Predicting protein decomposition: the case of aspartic-acid racemization kinetics
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DOI：
10.1098/rstb.1999.0359
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发表时间：
1999-01-29
影响因子：
6.3
通讯作者：
van Duin, ACT
中科院分区：
文献类型：
--
作者：
Collins, MJ;Waite, ER;van Duin, ACT
天冬氨酸（Asp）的非生物（D-）异构体相对于L-异构体的比例增加已被广泛用于考古学和地球化学中作为测年工具。该方法已被证明是有争议的，特别是当用于骨骼时。Asp外消旋化的非线性动力学已经促使了许多关于潜在机制的建议，并且已经导致使用数学变换，其使D-Asp相对于时间的增加线性化。使用一个例子，建议的初始快速阶段的天冬氨酸外消旋是由于天冬酰胺（Asn）的贡献，我们演示了如何一个简单的模型的降解和外消旋的Asn可以用来预测所观察到的动力学。通过形成环状琥珀酰亚胺（Asu）发生的肽结合Asx（Asn+Asp）外消旋化的更复杂模型可用于正确预测高温（95-140 ℃）下蛋白质中的Asx外消旋化动力学。该模型不能预测37 ℃时牙本质胶原的外消旋动力学。其原因是Asu的形成是高度构象依赖性的，并且预计在三螺旋胶原中发生得非常缓慢。由于构象强烈影响Asu形成的速度，因此Asx外消旋，使用外推从高温下，以估计其变性temperature.In考古骨蛋白的Asx的外消旋动力学被称为question. In的情况下，我们认为，D：L比的Asx反映了非螺旋螺旋螺旋胶原的比例，叠加的影响，更可溶的土地构象不受约束）肽的浸出。因此，骨中的外消旋动力学可能是不可预测的，并且提出的使用Asx外消旋来估计考古骨中DNA脱嘌呤的程度受到挑战。
The increase in proportion of the non-biological (D-) isomer of aspartic acid (Asp) relative to the L-isomer has been widely used in archaeology and geochemistry as a tool for dating. The method has proved controversial, particularly when used for bones. The non-linear kinetics of Asp racemization have prompted a number of suggestions as to the underlying mechanism(s) and have led to the use of mathematical transformations which linearize the increase in D-Asp with respect to time. Using one example, a suggestion that the initial rapid phase of Asp racemization is due to a contribution from asparagine (Asn), we demonstrate how a simple model of the degradation and racemization of Asn can be used to predict the observed kinetics. A more complex model of peptide bound Asx (Asn+Asp) racemization, which occurs via the formation of a cyclic succinimide (Asu), can be used to correctly predict Asx racemization kinetics in proteins at high temperatures (95-140 degrees C). The model fails to predict racemization kinetics in dentine collagen at 37 degrees C. The reason for this is that Asu formation is highly conformation dependent and is predicted to occur extremely slowly in triple helical collagen. As conformation strongly influences the rate of Asu formation and hence Asx racemization, the use of extrapolation from high temperatures to estimate racemization kinetics of Asx in proteins below their denaturation temperature is called into question.In the case of archaeological bone, we argue that the D:L ratio of Asx reflects the proportion of nonhelical to helical collagen, overlain by the effects of leaching of more soluble land conformationally unconstrained) peptides. Thus, racemization kinetics in bone are potentially unpredictable, and the proposed use of Asx racemization to estimate the extent of DNA depurination in archaeological bones is challenged.