Structural insights into the psychrophilic germinal protease PaGPR and its autoinhibitory loop

Chang Woo Lee,Saeyoung Lee,Chang-Sook Jeong,Jisub Hwang,Jeong Ho Chang,In-Geol Choi,T. Doohun Kim,HaJeung Park,Hye-Yeon Kim,Jun Hyuck Lee 한국미생물학회 2020 The journal of microbiology Vol.58 No.9

In spore forming microbes, germination protease (GPR) plays a key role in the initiation of the germination process. A critical step during germination is the degradation of small acidsoluble proteins (SASPs), which protect spore DNA from external stresses (UV, heat, low temperature, etc.). Inactive zymogen GPR can be activated by autoprocessing of the N-terminal pro-sequence domain. Activated GPR initiates the degradation of SASPs; however, the detailed mechanisms underlying the activation, catalysis, regulation, and substrate recognition of GPR remain elusive. In this study, we determined the crystal structure of GPR from Paenisporosarcina sp. TG-20 (PaGPR) in its inactive form at a resolution of 2.5 Å. Structural analysis showed that the active site of PaGPR is sterically occluded by an inhibitory loop region (residues 202–216). The N-terminal region interacts directly with the self-inhibitory loop region, suggesting that the removal of the N-terminal pro-sequence induces conformational changes, which lead to the release of the self-inhibitory loop region from the active site. In addition, comparative sequence and structural analyses revealed that PaGPR contains two highly conserved Asp residues (D123 and D182) in the active site, similar to the putative aspartic acid protease GPR from Bacillus megaterium. The catalytic domain structure of PaGPR also shares similarities with the sequentially non-homologous proteins HycI and HybD. HycI and HybD are metalloproteases that also contain two Asp (or Glu) residues in their active site, playing a role in metal binding. In summary, our results provide useful insights into the activation process of PaGPR and its active conformation.

비장동맥류의 임상적 경험

최상용,김영주,강인구,정석인,엄준원,조용걸,전성수,황정웅 대한혈관외과학회 2000 Vascular Specialist International Vol.16 No.1

Purpose: Splenic artery aneurysm is uncommon, but the increased frequency in use of arteriography, computed tomography, and ultrasonography has resulted in increasing clinical recognition of these lesions. This paper relates our experience in the outcome and management of aneurysms of the splenic artery. Methods: From January 1992 to October 1999, 12 patients were diagnosed with splenic artery aneurysms. They were retrospectively anslyzed. Results: The male to female ratio was 1: 4 and the mean age was 46.3 years. The mean of pregnancy history of all women was 3.0 and there were no pregnant women during operation. The associated diseases that might have caused the aneurysms were pancreatitis in 5 patients, portal hypertension in 1, operative trauma in 1, and ill defined pathogenesis in 5 patients. The size of the aneurysms was larger than 2 cm in all patients. The splenic artery aneurysms was located at distal in 9 patients, mid in 1, and proximal in 2 patients. 7 patients were treated surgically (aneurysmectomy without splenectomy in 1 patient, aneurysmectomy with splenectomy in 6 patients). Transcatheter embolization was used in 4 patients. One of them was treated with distal pancreatectomy after two months because of pancreatic pseudocyst. One patient without treatment died 2 years after diagnosis. Conclusion: Althougb surgery remains necessary in splenic artery aneurysms larger than 2 cm, transcatheter embolization is effective in initial treatment of the high risk group in splenic artery aneurysms.

Multi-institutional analysis of T3 subtypes and adjuvant radiotherapy effects in resected T3N0 non-small cell lung cancer patients

Choi, Yunseon,Lee, Ik Jae,Lee, Chang Young,Cho, Jae Ho,Choi, Won Hoon,Yoon, Hong In,Lee, Yun-Han,Lee, Chang Geol,Keum, Ki Chang,Chung, Kyung Young,Haam, Seok Jin,Paik, Hyo Chae,Lee, Kang Kyoo,Moon, Su The Korean Society for Radiation Oncology 2015 Radiation Oncology Journal Vol.33 No.2

Purpose: We evaluated the prognostic significance of T3 subtypes and the role of adjuvant radiotherapy in patients with resected the American Joint Committee on Cancer stage IIB T3N0M0 non-small cell lung cancer (NSCLC). Materials and Methods: T3N0 NSCLC patients who underwent resection from January 1990 to October 2009 (n = 102) were enrolled and categorized into 6 subgroups according to the extent of invasion: parietal pleura chest wall invasion, mediastinal pleural invasion, diaphragm invasion, separated tumor nodules in the same lobe, endobronchial tumor <2 cm distal to the carina, and tumor-associated collapse. Results: The median overall survival (OS) and disease-free survival (DFS) were 55.3 months and 51.2 months, respectively. In postoperative T3N0M0 patients, the tumor size was a significant prognostic factor for survival (OS, p = 0.035 and DFS, p = 0.035, respectively). Patients with endobronchial tumors within 2 cm of the carina also showed better OS and DFS than those in the other T3 subtypes (p = 0.018 and p = 0.016, respectively). However, adjuvant radiotherapy did not cause any improvement in survival (OS, p = 0.518 and DFS, p = 0.463, respectively). Only patients with mediastinal pleural invasion (n = 25) demonstrated improved OS and DFS after adjuvant radiotherapy (n = 18) (p = 0.012 and p = 0.040, respectively). Conclusion: The T3N0 NSCLC subtype that showed the most favorable prognosis is the one with endobronchial tumors within 2 cm of the carina. Adjuvant radiotherapy is not effective in improving survival outcome in resected T3N0 NSCLC.

Multi-institutional analysis of T3 subtypes and adjuvant radiotherapy effects in resected T3N0 non-small cell lung cancer patients

Yunseon Choi,MD,Ik Jae Lee,MD,Chang Young Lee,MD,Jae Ho Cho,MD,Won Hoon Choi,PhD,Hong In Yoon,MD,Yun-Han Lee,PhD,Chang Geol Lee,MD,Ki Chang Keum,MD,Kyung Young Chung,MD,Seok Jin Haam,MD,Hyo Chae Paik 대한방사선종양학회 2015 Radiation Oncology Journal Vol.33 No.2

Purpose: We evaluated the prognostic significance of T3 subtypes and the role of adjuvant radiotherapy in patients with resected the American Joint Committee on Cancer stage IIB T3N0M0 non-small cell lung cancer (NSCLC). Materials and Methods: T3N0 NSCLC patients who underwent resection from January 1990 to October 2009 (n = 102) were enrolled and categorized into 6 subgroups according to the extent of invasion: parietal pleura chest wall invasion, mediastinal pleural invasion, diaphragm invasion, separated tumor nodules in the same lobe, endobronchial tumor <2 cm distal to the carina, and tumor-associated collapse. Results: The median overall survival (OS) and disease-free survival (DFS) were 55.3 months and 51.2 months, respectively. In postoperative T3N0M0 patients, the tumor size was a significant prognostic factor for survival (OS, p = 0.035 and DFS, p = 0.035, respectively). Patients with endobronchial tumors within 2 cm of the carina also showed better OS and DFS than those in the other T3 subtypes (p = 0.018 and p = 0.016, respectively). However, adjuvant radiotherapy did not cause any improvement in survival (OS, p = 0.518 and DFS, p = 0.463, respectively). Only patients with mediastinal pleural invasion (n = 25) demonstrated improved OS and DFS after adjuvant radiotherapy (n = 18) (p = 0.012 and p = 0.040, respectively). Conclusion: The T3N0 NSCLC subtype that showed the most favorable prognosis is the one with endobronchial tumors within 2 cm of the carina. Adjuvant radiotherapy is not effective in improving survival outcome in resected T3N0 NSCLC

High substrate specificity of 3,6-anhydro-<small>L</small>-galactose dehydrogenase indicates its essentiality in the agar catabolism of a marine bacterium

Yu, Sora,Choi, In-Geol,Yun, Eun Ju,Kim, Kyoung Heon Elsevier 2018 Process biochemistry Vol.64 No.-

<P><B>Abstract</B></P> <P>3,6-Anhydro-<SMALL>L</SMALL>-galactose (AHG) is a rare sugar found in red macroalgae. The key metabolic steps in AHG catabolism involve its oxidation into 3,6-anhydrogalactonate (AHGA), followed by cycloisomerization of AHGA into 2-keto-3-deoxy-galactonate. These steps were recently discovered in a marine bacterium <I>Vibrio</I> sp. strain EJY3. In this study, we characterized NAD(P)<SUP>+</SUP>-dependent AHG dehydrogenase (AHGD) involved in the first step of AHG catabolism. AHGD displayed high substrate specificity for AHG, but showed no catalytic activity toward other aldehyde sugars, including D-form of AHG, glucose, and galactose. This high substrate specificity of AHGD may be associated with the unique chemical structure of its substrate AHG. Unlike other common aldehyde sugars, AHG mainly exists in its hydrated form under aqueous conditions. Growth of EJY3 in presence of AHG, agar, and <I>Gelidium amansii</I> but glucose, as the sole carbon source resulted in a significant increase in the AHGD activity of cell-free EJY3 lysates. Amino acid sequence analysis revealed that AHGD is highly homologous to other aldehyde dehydrogenases from agar-degrading bacteria, suggestive of its key role in agar-related metabolism in marine bacteria utilizing red macroalgae. Therefore, AHGD may serve as an important enzyme involved in the bioconversion of red macroalgal biomass to value-added chemicals.</P> <P><B>Highlights</B></P> <P> <UL> <LI> The oxidative activity of AHGD for AHG was confirmed by LC/MS. </LI> <LI> AHGD displayed high substrate specificity toward AHG. </LI> <LI> <I>Vibrio</I> sp. EJY3 under AHG or AHG-containing polymers showed high AHGD activity. </LI> <LI> AHGD is highly homologous to aldehyde dehydrogenases from agar-degrading bacteria. </LI> </UL> </P> <P><B>Graphical abstract</B></P> <P>[DISPLAY OMISSION]</P>

Chronic total occlusion intervention of the non-infarct-related artery in acute myocardial infarction patients: the Korean multicenter chronic total occlusion registry

Park, Ji Young,Choi, Byoung Geol,Rha, Seung-Woon,Kang, Tae Soo,Choi, Cheol Ung,Yu, Cheol Woong,Gwon, Hyeon-Cheol,Chae, In-Ho,Kim, Hyo-Soo,Park, Hun Sik,Lee, Seung-Hwan,Kim, Moo-Hyun,Hur, Seung-Ho,Jang Wolters Kluwer Health, Inc. All rights reserved. 2018 Coronary artery disease Vol.29 No.6

<P>BackgroundThe Korean chronic total occlusion (CTO) registry was collected prospectively from 26 cardiovascular centers since May 2007. The aim of this study is to investigate the impact of a successful staged percutaneous coronary intervention (PCI) of CTO lesions in acute myocardial infarction (AMI) patients on clinical outcomes.Patients and methodsAmong 2813 patients who underwent a staged PCI because of CTO lesions, 422 (15%) patients underwent primary PCI because of AMI. Among 422 patients, successful staged CTO-PCI was performed in 76%. The clinical outcomes were compared between the successful CTO-PCI group (n=321) and the failed CTO-PCI group (n=101). To adjust for potential confounders, a propensity score matching (PSM) analysis was carried out using the logistic regression model.ResultsAfter the PSM analysis, two propensity-matched groups (85 pairs, n=170) were generated and the baseline characteristics were balanced. The incidence of total death (P=0.029) and non-ST-segment elevation myocardial infarction (NSTEMI, P=0.043) at 1 year was higher in the failed CTO-PCI group. Multivariate regression showed that successful CTO-PCI was an independent predictor of preventing mortality (hazard ratio, 0.21, P=0.048). In the subgroup analysis, the Kaplan-Meier curve showed that successful CTO-PCI had a lower incidence of total death (log-rank=0.004) and cardiac death (log-rank=0.005) up to 1 year in NSTEMI patients. Cox-proportional analysis showed that successful CTO-PCI was beneficial in patients with NSTEMI, hypertension, and non-left-anterior descending artery lesion for preventing mortality.ConclusionIn this study, a staged successful CTO-PCI in AMI patients was associated with improved 1-year survival in the Korean population.</P>

Novel Insights into Agar Metabolism in Marine Heterotrophic Bacteria

파티라자 무디얀셀라게 둘리브 파티라자(Pathiraja Mudiyanselage Duleepa Pathiraja ),최인걸(In-Geol Choi) 고려대학교 생명자원연구소 2022 생명자원연구 Vol.30 No.-

대형 홍조류는 해양 생태계에서 해양 종속영양세균을 위한 풍부한 서식지를 제공하며, 한천은 대형 홍조류를 이루는 주요 구조적 다당류이다. 한천을 단일 탄소원으로 사용할 수 있는 해양 한천분해세균은 개방된 연안 해역에서 해양 초식 동물의 내장에 이르기까지 다양한 해양 환경에 분포한다. 한천분해세균에서의 한천의 해중합은 탄수화물 활성 효소(CAZymes)의 조합을 통해 이루어 진다. 한천분해세균의 유전체 구조에 대한 다양한 연구에서 이러한 탄수화물 활성 효소를 암호화하고 있는 유전자가 다당류 이용유전자좌(PUL)를 이루고 있음이 밝혀졌다. 한천 가수분해 효소(agarases)는 다음과 같이 분류되어질 수 있다. β-한천분해효소(GH16, GH50, GH86 및 GH118), α-한천분해효소(GH96), 네오아가로바이오스 가수분해효소(GH117) 및 한천분해 β-갈락토시데이스(GH2). 서로 다른 GH 계열에 속한 한천 가수분해효소들은 분자수준 기능, 구조 요소 및 촉매 메커니즘에 있어 고유한 특성을 나타낸다. 한천의 주요 성분 중 하나인 L-AHG는 희귀한 단당류이며, 그 대사 경로는 해양 한천분해세균에서만 발견되어 있다. 한천분해 시스템에 대한 최근의 연구들은 해양 종속영양세균이 가진 한천분해 경로의 보편적인 한천분해 효소 레퍼토리와 이의 진화를 보여주는 서열분석 데이터에 초점을 맞추고 있다. 또한, 올리고당의 수송 메커니즘과 PUL 유전자의 전사 조절을 이해하는 데에도 점점 더 많은 관심이 기울어지고 있다. 이 리뷰에서 우리는 한천 분해와 관련된 해양 종속영양세균의 유전체 구조에서부터 한천 분해의 대사 과정, 한천 가수분해 효소의 구조 및 기능 분석까지의 포괄적인 개요를 다룰 것이다. Agar is a key structural polysaccharide of red macroalgae which provides a rich habitat for marine heterotrophic bacteria in marine ecosystems. Marine agarolytic bacteria, that can use agar as the sole carbon source, are distributed in diverse marine environments from open coastal waters to the gut of marine herbivores. Agarolytic bacteria employ a combination of carbohydrate-active enzymes (CAZymes) for the depolymerization of agar. Extensive studies on the genomic architecture of the agarolytic bacteria suggested that genes encoding these CAZymes are arranged in polysaccharide utilization loci (PUL). Agar hydrolyzing enzymes (agarases) are categorized into; β-agarase (GH16, GH50, GH86, and GH118), α-agarase (GH96), neoagarooligosaccharide hydrolase (GH117), and agarolytic β-galactosidase (GH2). The molecular functionality, structural elements, and catalytic mechanisms of agarases belonging to different GH families show unique characteristics. L-AHG, one of the main constituents in agar, is a rare monosaccharide and its metabolic pathway is exclusively found in marine agarolytic bacteria. Recent trends in the agarolytic systems are mostly focused on the sequence data to visualize the universal agarolytic enzyme repertoire and the evolution of the agarolytic pathway in marine heterotrophic bacteria. In addition, increasing attention is paid to understanding the oligosaccharide transport mechanisms and transcriptional regulation of genes in PUL. In this review, we will cover a comprehensive overview of genomic architecture, structural and functional analysis of agar hydrolyzing enzymes, and agar metabolism in marine heterotrophic bacteria.

확정기여형 퇴직연금의 자산운용 성과 분석 및 정책적 시사점

성주호 ( Joo Ho Sung ),김인걸 ( In Geol Kim ),최윤호 ( Yun Ho Choi ) 한국연금학회 2013 연금연구 Vol.3 No.2

본 연구에서는 금융시장 환경변화인 임금상승율, 자산할당방법, 투자기간에 따른 확정기여형 퇴직 연금자산운용 결과에 대한 사후검증과 예측을 통해 자산운용의 수익성을 살펴보고 있다. 이를 위하여 한국은행의 국고채 과거 금리지표(2005-2012), 한국신용평가(KIS)의 채권의 과거 수익률(2005-2012) 그리고 주식의 경우는 KOSPI200을 사용하였다. 적용되는 자산운용 시나리오는 실무에서 보편적으로 적용하는 12개를 설정하였다. 즉, 확정금리상품에 대해 5가지 그리고 주식과 채권의 혼합비율에 따라 7가지 자산할당방식을 각각 가정하였다. 이에 근거한 사후분석 결과로는 전체적으로 확정금리형 상품에 비해 주식·채권 혼합형이 상대적으로 높은 수익률을 나타내고 있다. 주요 시사점으로는 현행 확정기여형(DC) 자산운용규제는 금융환경 변화에 대한 소극적 자산운용으로 규정할 수 있다. 따라서 향후 일정수준 이상 적극적으로 자산운용을 할 수 있도록 현행 규제를 완화, 보완할 필요성이 있다. In this study, we examined the investment performance of DC retirement pension funds in Korea financial market using ex-post analysis with experienced salary rates and returns during 2005-2012. Further, for testing the efficiency of current asset allocation, we used the yields on bonds provided by KIS(Korea Investors Service) and KOSPI 200 index and guaranteed market interest rates. In particular, 5 different scenarios investing in guaranteed fixed deposit products and 7 different scenarios investing in stocks and bonds are set up for testing. And then, their investment performances each are compared in the same conditions. We find out that in general, investing in stocks and bonds outperformed investing in guaranteed fixed deposit in Korea financial market, as in global market. Hence, we would suggest that current investment regulations have to be modified following global standards and practices: that is, in a direction to weakening the current DC asset allocation regulation.

Crystal structure analysis of 3,6-anhydro-<small>L</small>-galactonate cycloisomerase suggests emergence of novel substrate specificity in the enolase superfamily

Lee, Saeyoung,Kim, Kyoung Heon,Kim, Hye-Yeon,Choi, In-Geol Elsevier 2017 Biochemical and biophysical research communication Vol. No.

<P><B>Abstract</B></P> <P>3,6-Anydro-<SMALL>L</SMALL>-galatonate cycloisomerase (ACI) catalyzes the cycloisomerization of a 3,6-anhydro-<SMALL>L</SMALL>-galactonic acid known as a novel metabolite in agarolytic bacteria. Here, we present 3-D structures of ACI from <I>Vibrio</I> sp. strain EJY3 (<I>Vej</I>ACI) in native and mutant forms at 2.2 Å and 2.6 Å resolutions, respectively. The enzyme belongs to the mandelate racemase subgroup of the enolase superfamily catalyzing common β-elimination reactions by α-carbon deprotonation of substrates. The structure of <I>Vej</I>ACI revealed a notable 20s loop region in the capping domain, which can be a highly conserved structural motif in ACI homologs of agar metabolism. By comparing mutant (m<I>Vej</I>AC/H300 N) and native <I>Vej</I>ACI structures, we identified a conformational change of Ile142 in <I>Vej</I>ACI that causes spatial expansion in the binding pocket. These observations imply that Ile142 and the 20s loop play important roles in enzymatic reactivity and substrate specificity. The structural phylogenetic analysis of the enolase superfamily including ACIs revealed sequential, structural, and functional relationships related to the emergence of novel substrate specificity.</P> <P><B>Highlights</B></P> <P> <UL> <LI> The 3D-structures of a key anhydro-sugar metabolic enzyme in native and mutant forms. </LI> <LI> A conformational change of Ile142 makes a spatial expansion of the active site. </LI> <LI> The 20s loop region is a critical structural motif for substrate specificity. </LI> <LI> The reaction mechanism is proposed by critical residues in the binding pocket. </LI> </UL> </P>

악하선 암의 치료성적과 예후인자

임치영(Chi Young Lim),남기현(Kee Hyun Nam),이잔디(Jan Dee Lee),장항석(Hang Seok Chang),정웅윤(Woong Youn Chung),차인호(In Ho Cha),이창걸(Chang Geol Lee),최은창(Eun Chan Choi),박정수(Cheong Soo Park) 대한두경부종양학회 2005 대한두경부 종양학회지 Vol.21 No.2

Purpose: Submandibular gland tumor is rare, less than 6% of head and neck tumor. The purpose of this article is to analysis the clinical experience and treatment outcomes of malignant submandibular gland tumor, suggesting a guideline of management. Methods: We retrospectively evaluated 26 patients who underwent operation for malignant submandibular gland tumor at Severence hospital between 1986 and 2004. Statistical analysis was performed by Kaplan-Meier method, log rank test, Chi-square test, Fisher's exact test using SPSS v12.0 for Windows. Results: They consisted of 18 males and 8 females whose median age was 47 years(range: 20-71). 10 cases of adenocystic carcinoma, 8 cases of carcinoma ex pleomorphic adenoma, 4 cases of mucoepidermoid carcinoma, 1 case each for acinic cell carcinoma, undifferentiated carcinoma, adeno carcinoma, epithelioid hemangioendothelioma. Sialoadenectomy only was performed in 10 cases(36.5%) and sialoadenectomy with neck node dissection was performed in 16 cases(63.5%). Adjuvant radiotherapy was done in 22 cases(84.6%). 10 year disease free survival rate for malignant submandibular gland tumor was 63.1 % and 10 year overall survival rate for malignant submandibular gland tumor was 70.1%. In univariate analysis, prognostic factors affecting recurrence of malignant submandibular gland tumor was initially papable lateral neck node in physical examination and metastasis of lateral neck node in pathologic confirmation. The prognostic factors affecting survival of malignant submandibular gland tumor was tumor size, TNM stage, recurrence and type of recurrence. Conclusion: In this study, prognostic factors affecting recurrence of malignant submandibular gland tumor was initially papable lateral neck node in physical examination and metastasis of lateral neck node in pathologic confirmation. The prognostic factors affecting survival of malignant submandibular gland tumor was tumor size, TNM stage, recurrence and type of recurrence. To prevent recurrence and to improve survival, early diagnosis and aggressive surgery must be considered.