In an effort to elucidate and engineer interactions in type II nonribosomal peptide synthetases, we analyzed biomolecular recognition between the essential peptidyl carrier proteins and adenylation domains using nuclear magnetic resonance (NMR) spectroscopy, molecular dynamics, and mutational studies. Three peptidyl carrier proteins, PigG, PltL, and RedO, in addition to their cognate adenylation domains, PigI, PltF, and RedM, were investigated for their cross-species activity. Of the three peptidyl carrier proteins, only PigG showed substantial cross-pathway activity. Characterization of the novel NMR solution structure of holo-PigG and molecular dynamics simulations of holo-PltL and holo-PigG revealed differences in structures and dynamics of these carrier proteins. NMR titration experiments revealed perturbations of the chemical shifts of the loop 1 residues of these peptidyl carrier proteins upon their interaction with the adenylation domain. These experiments revealed a key region for the protein-protein interaction. Mutational studies supported the role of loop 1 in molecular recognition, as mutations to this region of the peptidyl carrier proteins significantly modulated their activities.

Cancer treatment can trigger or exacerbate health-related socioeconomic risks (HRSR; food/housing insecurity, transportation/utilities difficulties, and interpersonal violence). The American Cancer Society and National Cancer Institute recommend HRSR screening and referral, but little research has examined the perceptions of patients with cancer on the appropriateness of HRSR screening in healthcare settings. We examined whether HRSR status, desire for assistance with HRSRs, and sociodemographic and health care-related factors were associated with perceived appropriateness of HRSR screening in health care settings and comfort with HRSR documentation in electronic health records (EHR). A convenience sample of adult patients with cancer at two outpatient clinics completed self-administered surveys. We used χ ² and Fisher exact tests to test for significant associations. The sample included 154 patients (72% female, 90% ages 45 years or older). Thirty-six percent reported ≥1 HRSRs and 27% desired assistance with HRSRs. Overall, 80% thought it was appropriate to assess for HRSRs in health care settings. The distributions of HRSR status and sociodemographic characteristics were similar among people who perceived screening to be appropriate and those who did not. Participants who perceived screening as appropriate were three times as likely to report prior experience with HRSR screening (31% vs. 10%, P = 0.01). Moreover, 60% felt comfortable having HRSRs documented in the EHR. Comfort with EHR documentation of HRSRs was significantly higher among patients desiring assistance with HRSRs (78%) compared with those who did not (53%, P < 0.01). While initiatives for HRSR screening are likely to be seen by patients with cancer as appropriate, concerns may remain over electronic documentation of HRSRs.

Significance

National organizations recommend addressing HRSRs such as food/housing insecurity, transportation/utilities difficulties, and interpersonal violence among patients with cancer. In our study, most patients with cancer perceived screening for HRSRs in clinical settings as appropriate. Meanwhile, concerns may remain over the documentation of HRSRs in EHRs.