ABSTRACT
We report a case of nonaccidental trauma (NAT) involving a 23-month-old boy who presented with seizures, acute subarachnoid hemorrhage, and acute subdural hemorrhage. Ophthalmologic examination showed bilateral intraretinal hemorrhages. Further evaluation revealed that he had bilateral thoracolumbar paravertebral calcifications. The Children's Protective Services agency was involved in the case. The child was discharged to an inpatient rehabilitation facility. Vertebral fracture associated with paravertebral calcification has been reported as a sign of NAT. This case was unique because our patient had paravertebral calcifications without vertebral fracture. Paravertebral calcification alone could serve as an indicator of NAT.
Subject(s)
Battered Child Syndrome/diagnostic imaging , Calcification, Physiologic , Child Abuse/diagnosis , Intracranial Hemorrhage, Traumatic/diagnostic imaging , Soft Tissue Injuries/etiology , Battered Child Syndrome/diagnosis , Humans , Infant , Male , Retinal Hemorrhage/etiology , Seizures/etiologyABSTRACT
S-adenosylmethionine (AdoMet)-based methylation is integral to metabolism and signaling. AdoMet-dependent methyltransferases belong to multiple distinct classes and share a catalytic mechanism that arose through convergent evolution; however, fundamental determinants underlying this shared methyl transfer mechanism remain undefined. A survey of high-resolution crystal structures reveals that unconventional carbon-oxygen (CH···O) hydrogen bonds coordinate the AdoMet methyl group in different methyltransferases irrespective of their class, active site structure, or cofactor binding conformation. Corroborating these observations, quantum chemistry calculations demonstrate that these charged interactions formed by the AdoMet sulfonium cation are stronger than typical CH···O hydrogen bonds. Biochemical and structural studies using a model lysine methyltransferase and an active site mutant that abolishes CH···O hydrogen bonding to AdoMet illustrate that these interactions are important for high-affinity AdoMet binding and transition-state stabilization. Further, crystallographic and NMR dynamics experiments of the wild-type enzyme demonstrate that the CH···O hydrogen bonds constrain the motion of the AdoMet methyl group, potentially facilitating its alignment during catalysis. Collectively, the experimental findings with the model methyltransferase and structural survey imply that methyl CH···O hydrogen bonding represents a convergent evolutionary feature of AdoMet-dependent methyltransferases, mediating a universal mechanism for methyl transfer.
